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Bending the Curve Trial by Trial
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2011–2019

Immunotherapy

Visual dialect: cellular and organic forms, bioluminescence. Eras are a storytelling frame, not a historical claim.

  1. 2011 · Understanding · Acute myeloid leukaemia (including APL)

    Early death in APL: population data and pooled trial cohorts

    A 2011 analysis of US cancer-registry data found that about 17 in 100 people diagnosed with acute promyelocytic leukemia between 1992 and 2007 died early, a rate the authors said appeared higher than commonly reported in clinical trials. A 2025 analysis combining two trials and four European registries reported early death in about 6 in 100.

    Park 2011 (SEER, 1992-2007, 1400 patients): early death 17.3% overall and 24.2% at age 55 or older, with only a modest change over time; 3-year survival improved from 54.6% (1992-1995) to 70.1% (2002-2007), 46.4% at age 55 or older. Voso 2025 (HARMONY, trials plus registries, 1999-2022): early death 85 of 1438 (5.9%) at a median of 9 days; associated with age (OR 1.06, CI 1.04-1.08) and high Sanz risk score (OR 4.65, CI 2.55-8.51).

  2. 2011 · Understanding · Bladder cancer

    Smoking and bladder cancer risk in a large US cohort

    In a large US cohort followed from 1995 to 2006, current smokers had about four times, and former smokers about twice, the bladder cancer risk of people who never smoked. The authors found higher relative risks than in earlier US cohorts and estimated that about half of cases in both sexes were attributable to smoking.

    NIH-AARP cohort, follow-up 1995-2006 (about 4.5 million person-years): bladder cancer in 3896 men and 627 women. Versus never smokers (39.8 per 100000 person-years), hazard ratio 2.22 (95% CI 2.03 to 2.44) for former and 4.06 (3.66 to 4.50) for current smokers. Summary relative risk for current smoking in 7 earlier cohorts (begun 1963-1987) 2.94 (2.45 to 3.54). Population attributable risk for ever smoking 0.50 in men, 0.52 in women.

  3. 2011 · Treatment · Breast cancer

    CLEOPATRA: pertuzumab added to trastuzumab and docetaxel

    A large trial in people starting treatment for HER2-positive metastatic breast cancer compared adding a second antibody, pertuzumab, to trastuzumab and docetaxel against adding a placebo. Progression took longer with pertuzumab and, in later reports, survival was longer. The US regulator approved the combination in June 2012.

    Double-blind phase 3, 808 patients, first-line HER2-positive metastatic disease: pertuzumab vs placebo plus trastuzumab and docetaxel. Independently assessed median PFS 18.5 vs 12.4 months (HR 0.62; 95% CI 0.51 to 0.75; P<0.001). Final overall survival (median follow-up 50 months): 56.5 vs 40.8 months (HR 0.68; 95% CI 0.56 to 0.84). End-of-study descriptive analysis: median OS 57.1 vs 40.8 months; 8-year OS 37% vs 23%.

  4. 2011 · Reversal · Breast cancer

    FDA withdraws bevacizumab for metastatic breast cancer (2011)

    In 2008 the US regulator approved bevacizumab with paclitaxel as first treatment for metastatic breast cancer because it delayed cancer growth, on condition that further trials confirm the benefit. Those trials showed smaller gains and no survival advantage. The US indication was withdrawn in November 2011. The European listing for this use remains.

    E2100 (N=722; paclitaxel with or without bevacizumab): median PFS 11.8 vs 5.9 months (HR 0.60; P<0.001); median OS 26.7 vs 25.2 months (HR 0.88; P = 0.16). AVADO (docetaxel; bevacizumab 15 mg/kg): median PFS 10.1 vs 8.2 months (HR 0.77; P = 0.006, unstratified). RIBBON-1: PFS HR 0.69 (capecitabine) and 0.64 (taxane or anthracycline cohort). Accelerated approval 22 February 2008; withdrawal decision 18 November 2011.

  5. 2011 · Treatment · Chronic lymphocytic leukaemia

    CAR T cells in CLL: 2011 report to 2024 liso-cel approval

    In 2011 doctors reported a complete remission in a patient with refractory CLL treated with CAR T cells made from the person's own T cells. In a 2023 trial of people whose CLL had progressed on a BTK inhibitor and venetoclax, fewer than one in five had a complete response or remission. The FDA gave accelerated approval in March 2024.

    Porter 2011: CD19-directed 4-1BB CAR T cells in a patient with refractory CLL; complete remission ongoing at 10 months; delayed tumour lysis syndrome. TRANSCEND CLL 004 (phase 1-2, single arm; 117 treated after a BTK inhibitor, 70 also after venetoclax): in the primary efficacy analysis set at dose level 2 (49 patients), CR/CRi rate 18% (95% CI 9 to 32; P=0.0006). Grade 3 CRS 9%, grade 3 neurological events 18%. FDA accelerated approval 14 March 2024.

  6. 2011 · Detection · Endometrial cancer

    Sentinel node biopsy tested as an alternative to lymphadenectomy

    Three prospective studies checked how well sampling only the first draining lymph nodes (the sentinel nodes) finds cancer spread, with removal of many nodes as the reference. In each, most women with lymph-node spread were picked up by the sentinel nodes. None was designed to test survival or recurrence after skipping full node removal.

    Prospective non-randomised cohorts with lymphadenectomy as the reference and no survival endpoints. SENTI-ENDO (133 enrolled, stage I-II; primary endpoint NPV per hemipelvis 100%, 95% CI 95-100): per patient, sensitivity 84% (62-95), NPV 97% (91-99). FIRES (385 enrolled, indocyanine green): sensitivity 97.2% (85.0-100), NPV 99.6% (97.9-100). SENTOR (156 enrolled, grade 2 endometrioid or high-grade): sensitivity 96% (81-100), NPV 99% (96-100).

  7. 2011 · Treatment · Hodgkin lymphoma

    Brentuximab vedotin approved for relapsed Hodgkin lymphoma

    In 2011 the US regulator gave accelerated approval to brentuximab vedotin, a CD30-targeted antibody-drug conjugate, for Hodgkin lymphoma that returned after a stem-cell transplant, or after two chemotherapy regimens in people unable to have one. In the pivotal post-transplant study, three in four people had their cancer shrink and about one in three had no detectable disease.

    FDA accelerated approval, 19 August 2011: Hodgkin lymphoma after failure of ASCT, or after at least two multi-agent regimens in non-candidates. Pivotal single-arm phase 2 after ASCT (n=102; 1.8 mg/kg every 3 weeks): ORR 75%, complete remission 34%, median PFS 5.6 months. Phase 1 (n=45): maximum tolerated dose 1.8 mg/kg every 3 weeks; 6 of 12 patients at that dose responded.

  8. 2011 · Detection · Lung cancer

    NLST: low-dose CT screening lowers lung-cancer mortality

    The US National Lung Screening Trial gave about 53,000 older people with a heavy smoking history three yearly scans, either low-dose CT or a chest X-ray. Deaths from lung cancer were about one in five lower after CT screening. Many scans were positive, and nearly all of those positive results were false alarms.

    Randomised trial at 33 US centres: 53,454 people aged 55-74 with at least 30 pack-years were assigned to three annual screens with low-dose CT or chest radiography. Lung-cancer mortality (primary) was 247 vs 309 per 100,000 person-years (CT vs radiography), a 20.0% relative reduction (95% CI 6.8-26.7; P=0.004). All-cause mortality fell 6.7% (95% CI 1.2-13.6; P=0.02). Screens were positive in 24.2% vs 6.9%; 96.4% vs 94.5% of positives were false.

  9. 2011 · Treatment · Melanoma

    BRAF inhibition: vemurafenib (BRIM-3) and companions, 2011-2012

    In melanoma carrying a BRAF V600E mutation, vemurafenib was compared with dacarbazine chemotherapy. Survival at six months and the time before progression were better with vemurafenib, and the FDA approved it in August 2011. Dabrafenib and trametinib each improved progression-free survival over chemotherapy in 2012 reports and were approved as single agents in 2013.

    BRIM-3 (n=675, untreated BRAF V600E): vemurafenib 960 mg twice daily vs dacarbazine; 6-month OS 84% vs 64% (HR for death 0.37; 95% CI 0.26 to 0.55); median PFS 5.3 vs 1.6 months (HR 0.26); response 48% vs 5%. BREAK-3 (n=250): dabrafenib vs dacarbazine, median PFS 5.1 vs 2.7 months (HR 0.30). METRIC (n=322): trametinib vs chemotherapy, median PFS 4.8 vs 1.5 months (HR 0.45).

  10. 2011 · Treatment · Ovarian cancer

    Bevacizumab added to first-line chemotherapy: GOG-218 and ICON7

    Two large randomised trials added bevacizumab to carboplatin and paclitaxel for newly diagnosed ovarian cancer. Both reported longer progression-free survival; in GOG-218 the median gain was about four months when bevacizumab continued after chemotherapy. Neither showed longer overall survival in the full study population, and bevacizumab was associated with more high blood pressure.

    GOG-218 (N=1873, placebo-controlled): median PFS 10.3 (control), 11.2 (bevacizumab initiation) and 14.1 months (throughout); HR 0.717 (95% CI 0.625-0.824) for throughout. Final OS HR 0.96 (0.85-1.09). ICON7 (N=1528, open label): PFS HR 0.81 (0.70-0.94); OS restricted mean 44.6 (chemotherapy) vs 45.5 months (bevacizumab; p=0.85); a poor-prognosis subgroup analysis was exploratory.

  11. 2011 · Detection · Ovarian cancer

    Ovarian cancer screening: PLCO and UKCTOCS find no mortality reduction

    Two large randomised trials tested yearly screening with a CA-125 blood test, a vaginal ultrasound or both in women without symptoms. The US trial (2011) and the UK trial (long-term report, 2021) did not find a significant fall in deaths from ovarian cancer. The US trial recorded serious complications after false-positive results.

    PLCO (78,216 women aged 55 to 74): ovarian cancer mortality rate ratio 1.18 (95% CI 0.82 to 1.71), 118 vs 100 deaths; 163 of 1080 women who had surgery after a false-positive result (15%) had at least one serious complication. UKCTOCS (202,638 women aged 50 to 74): deaths from ovarian or tubal cancer 296 (multimodal screening), 291 (ultrasound) and 619 (no screening) at a median 16.3 years; no significant reduction (P=0.58 and P=0.36).

  12. 2011 · Understanding · Ovarian cancer

    Inherited mutations are common in ovarian cancer: test all patients

    From 2011, gene-sequencing studies found that a substantial share of women with ovarian, fallopian tube or peritoneal cancer carry an inherited harmful gene change, often with no family history of the disease. The 2011 study found about one in four among 360 women. A 2020 ASCO guideline advises genetic testing for every woman with epithelial ovarian cancer.

    Walsh 2011 (360 women, consecutive, not selected for age or family history): germline loss-of-function mutations in 24%, BRCA1 or BRCA2 in 18%; over 30% of carriers had no family history of breast or ovarian carcinoma. Alsop 2012 (1,001 non-mucinous cases): germline BRCA1 or BRCA2 in 14.1%, 44% of carriers without family history. Norquist 2016 (1915 women): 18% pathogenic germline mutations, 15% in BRCA1 or BRCA2. ASCO 2020 recommends germline testing for all women with epithelial ovarian cancer.

  13. 2011 · Treatment · Pancreatic cancer

    FOLFIRINOX versus gemcitabine: PRODIGE 4 / ACCORD 11

    In a French trial of 342 people with spread pancreatic cancer who were well enough to be up and about, a four-drug regimen called FOLFIRINOX was compared with gemcitabine. Median survival was about 11 months with FOLFIRINOX and about 7 months with gemcitabine, with more side effects.

    PRODIGE 4 / ACCORD 11, phase 2/3: 342 patients with metastatic pancreatic cancer, ECOG 0-1, FOLFIRINOX vs gemcitabine. Median OS 11.1 vs 6.8 months, HR 0.57 (95% CI 0.45-0.73; P<0.001). Median PFS 6.4 vs 3.3 months, HR 0.47 (0.37-0.59). ORR 31.6% vs 9.4%. Febrile neutropenia 5.4% with FOLFIRINOX. Authors: an option for patients with good performance status.

  14. 2011 · Treatment · Prostate cancer

    Abiraterone after docetaxel improves survival (COU-AA-301)

    Abiraterone, which blocks androgen production, was tested with prednisone in 1,195 men whose metastatic castration-resistant prostate cancer had progressed after docetaxel. At the first analysis, median survival was 14.8 months with abiraterone against 10.9 months with placebo. The FDA approved it on 28 April 2011.

    COU-AA-301: randomized (2:1), double-blind phase 3, n=1195, post-docetaxel mCRPC; abiraterone acetate 1000 mg plus prednisone versus placebo plus prednisone. Interim OS (median follow-up 12.8 months): 14.8 versus 10.9 months, HR 0.65 (95% CI 0.54-0.77; P<0.001). Final OS before crossover (median follow-up 20.2 months): 15.8 versus 11.2 months, HR 0.74 (0.64-0.86). Radiologic PFS 5.6 versus 3.6 months. Mineralocorticoid-related adverse events were more frequent with abiraterone.

  15. 2011 · Treatment · Thyroid cancer

    ZETA: vandetanib for advanced medullary thyroid cancer

    In a trial of 331 people with advanced medullary thyroid cancer, those given the pill vandetanib went longer without their cancer growing than those given placebo; the risk of progression or death was roughly halved. The FDA approved vandetanib in 2011. Overall survival data were too early to judge.

    ZETA, phase 3, double-blind: 331 patients with advanced MTC randomised 2:1 to vandetanib 300 mg/day (231) or placebo (100). Primary endpoint PFS by independent central RECIST review: HR 0.46 (95% CI 0.31-0.69), P<.001, median follow-up 24 months. OS immature: HR 0.89 (0.48-1.65). Post hoc, symptomatic and progressive subgroup (184 patients): PFS HR 0.43 (0.28-0.64).

  16. 2012 · Treatment · Bladder cancer

    BC2001: chemotherapy added to radiotherapy for bladder preservation

    Radiotherapy is an alternative to bladder removal for some people with muscle-invasive bladder cancer. In the BC2001 trial, adding two chemotherapy drugs to radiotherapy improved control of the cancer in the bladder area: at two years 67% were alive and free of locoregional (bladder and pelvic) disease versus 54%. Differences in survival were not statistically significant.

    BC2001 (phase 3, 2 x 2 factorial; 360 randomised to radiotherapy 178 vs radiotherapy plus fluorouracil and mitomycin C 182). 2-year locoregional DFS 67% vs 54% (HR 0.68, 95% CI 0.48-0.96); 5-year OS 48% vs 35% (HR 0.82, 0.63-1.09, P=0.16). At 9.9 years' median follow-up (ITT): locoregional control HR 0.61 (0.43-0.86); OS HR 0.88 (0.69-1.13); 5-year cystectomy rate 14% vs 22%.

  17. c. 2012 · Understanding · Bladder cancer

    BCG shortages from about 2012 limit intravesical therapy

    BCG, a critical treatment for higher-risk non-muscle-invasive bladder cancer, ran short twice within about three years, the second time announced in 2014, according to a urologist's 2017 commentary. In a French single-centre study, people affected by the 2012 to 2014 shortage more often could not complete BCG induction and maintenance.

    Commentary (Messing 2017) plus a retrospective single-centre French study of high-risk NMIBC. In the study, BCG induction could not be completed in 20.8% of patients impacted by the 2012-2014 Connaught-strain shortage versus 5.3% of those not impacted (P=0.02); maintenance was incomplete in 56.6% versus 37.5% (P=0.047). No significant difference in recurrence-free, progression-free, overall or specific survival; cystectomy rate higher in the impacted group.

  18. 2012 · Treatment · Breast cancer

    EMILIA: trastuzumab emtansine versus lapatinib plus capecitabine

    In people with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane, trastuzumab emtansine, an antibody linked to a chemotherapy drug, delayed progression and lengthened survival compared with lapatinib plus capecitabine. Grade 3 or 4 side effects were less frequent overall.

    Randomised trial (991 patients previously treated with trastuzumab and a taxane): trastuzumab emtansine vs lapatinib plus capecitabine. Median PFS (independent review) 9.6 vs 6.4 months (HR 0.65; 95% CI 0.55 to 0.77; P<0.001). Median OS at the second interim analysis 30.9 vs 25.1 months (HR 0.68; 95% CI 0.55 to 0.85; P<0.001). Response rate 43.6% vs 30.8%. Grade 3 or 4 adverse events 41% vs 57%.

  19. 2012 · Detection · Breast cancer

    Screening, overdiagnosis and the benefit-harm debate

    Estimates of how much mammography screening lowers breast cancer deaths, and of how many cancers it finds that would never have caused harm (overdiagnosis), differ between reviews and trials. The differences reflect the trials chosen, the methods and the assumptions made, and the balance remains debated.

    Estimates differ by method. UK Independent Panel 2012, meta-analysis of 11 randomised trials: breast cancer mortality RR 0.80 (95% CI 0.73-0.89); excess incidence 11% of cancers in the invited group long term. Cochrane 2013: RR 0.90 (0.79-1.02) in 3 adequately randomised trials, 0.81 across 7. CNBSS 25 years: HR 1.05 (0.85-1.30) for death from cancers diagnosed in the screening period; 22% of screen-detected invasive cancers overdiagnosed. Welch 2016 (SEER, age 40+): 132 overdiagnosed cases per 100,000 women.

  20. 2012 · Understanding · Childhood acute lymphoblastic leukemia (ALL)

    Childhood ALL survival trends 1990-2005 (COG)

    A Children's Oncology Group analysis of 21,626 young people treated on its ALL trials found that five-year survival rose from about 84 in 100 in 1990-1994 to about 90 in 100 in 2000-2005. Survival changed little for infants. NCI's fact sheet separately reports a rise from 57 in 100 in 1975 to 92 in 100 in 2014-2020.

    COG analysis of 21,626 persons aged 0 to 22 years enrolled on ALL trials 1990-2005 (55.8% of estimated US cases). Five-year survival rose from 83.7% (1990-1994) to 90.4% (2000-2005), P<.001; all subgroups improved except infants (age 1 year or younger). Deaths after relapse or progression decreased and treatment-related deaths increased; 36% of deaths occurred in NCI standard-risk patients. Separate NCI fact sheet: ALL 5-year survival 57% (1975) to 92.3% (2014-2020).

  21. 2012 · Treatment · Chronic myeloid leukemia

    Ponatinib: activity against T315I (PACE)

    Ponatinib was approved in the US in December 2012 for people whose CML or Philadelphia-chromosome-positive ALL no longer responded to, or could not tolerate, other kinase inhibitors. In the PACE trial, 56% of people with chronic-phase CML had a major cytogenetic response, including 70% of those with the T315I mutation. Serious arterial blood-clot events occurred in 9% of all participants.

    PACE, single-arm phase 2 (449 heavily pretreated patients; ponatinib 45 mg daily; median follow-up 15 months). Chronic phase (267 evaluable): MCyR 56% (51% resistant or intolerant; 70% T315I), CCyR 46%, MMR 34%. Serious arterial thrombotic events 9% (3% treatment-related). Final analysis (56.8 months): MCyR 60%, MMR 40%, 5-year OS 73%, cumulative arterial occlusive events 31%. OPTIC (n=283): BCR-ABL1 IS ≤1% at 12 months 44.1%, 29.0%, 23.1% by 45, 30, 15 mg start.

  22. 2012 · Treatment · Chronic myeloid leukemia

    Bosutinib: from a missed first-line endpoint (BELA) to BFORE

    In the BELA trial, bosutinib did not beat imatinib on its main goal, complete cytogenetic response at 12 months, in newly diagnosed chronic-phase CML. In the later BFORE trial, whose main goal was major molecular response, rates were higher with bosutinib (about 47% against 37%). The FDA approved it for previously treated people in 2012 and new diagnoses in 2017.

    BELA (n=502): CCyR at 12 months 70% (95% CI 64-76) with bosutinib 500 mg vs 68% (62-74) with imatinib 400 mg, P=0.601 (primary endpoint not met); MMR 41% vs 27% (P<0.001). BFORE (n=536; efficacy population 246 vs 241): MMR at 12 months (primary) 47.2% vs 36.9% (P=0.02); CCyR by 12 months 77.2% vs 66.4% (P=0.0075). Grade 3 or higher ALT increase 19.0% vs 1.5%.

  23. 2012 · Treatment · Colorectal cancer

    Regorafenib for previously treated metastatic CRC (CORRECT)

    For people whose bowel cancer had kept growing after all standard treatments, a placebo-controlled trial tested regorafenib, a tablet that blocks several growth signals. Survival was longer than with placebo, by a little over a month, at the cost of frequent side effects such as hand-foot skin reaction.

    Double-blind phase 3 trial, 760 patients with metastatic colorectal cancer progressing during or within 3 months after the last standard therapy, randomised 2:1 to regorafenib (n=505) or placebo (n=255), both with best supportive care. Median OS 6.4 vs 5.0 months (HR 0.77, 95% CI 0.64-0.94; one-sided P=0.0052; preplanned interim analysis). Hand-foot skin reaction of grade 3 or higher: 17% with regorafenib.

  24. 2012 · Understanding · Hepatocellular carcinoma

    Hepatitis C clearance and HCC: interferon-era SVR, then DAA debate

    A long-term study of people with hepatitis C and advanced liver scarring found less liver cancer over ten years in those whose virus was cleared by treatment. After newer antiviral tablets arrived, a small study of people with previously treated liver cancer reported frequent early return, while larger cohorts of new cancers reported lower risk with viral clearance or treatment.

    Four observational cohorts, each analysed on its own terms. Interferon era (n=530, advanced fibrosis): 10-year HCC incidence 5.1% with SVR versus 21.8% without. DAA era: Reig reported radiologic recurrence in 27.6% of 58 patients with treated HCC (median follow-up 5.7 months, no control group); US Veterans cohort adjusted HR 0.28 for HCC with SVR; French Hepather adjusted HR 0.66 for HCC with DAA exposure (unadjusted 2.77).

  25. 2012 · Treatment · Melanoma

    Anti-PD-1 in melanoma: phase 1 results to FDA approvals (2012-2014)

    Early studies of antibodies against PD-1 reported responses in some people with advanced melanoma, with some lasting a year or more. Randomised trials in melanoma that had progressed after ipilimumab followed. The FDA granted accelerated approval to pembrolizumab in September 2014 and nivolumab in December 2014.

    Phase 1 nivolumab (n=296 treated, several tumour types): melanoma objective response 28% (26 of 94). Phase 1 lambrolizumab (135 melanoma patients treated): confirmed response 38% (44 of 117 by central review), 52% at 10 mg/kg every 2 weeks. KEYNOTE-002 (n=540, post-ipilimumab, phase 2): PFS HR 0.57 (2 mg/kg) and 0.50 (10 mg/kg) vs chemotherapy. CheckMate 037 (n=405): response 31.7% vs 10.6%, first interim analysis. FDA accelerated approvals 4 September and 22 December 2014.

  26. 2012 · Treatment · Multiple myeloma

    Lenalidomide maintenance after autologous transplant

    After a stem cell transplant, people with myeloma were randomly given lenalidomide or placebo until the disease progressed. In two trials, progression took longer with lenalidomide, but second cancers were more frequent. One trial reported fewer deaths with lenalidomide; the other found similar survival at four years. A pooled analysis of three trials reported longer survival.

    IFM 2005-02 (n=614, age under 65): median PFS (primary) 41 versus 23 months, HR 0.50 (P<0.001); second primary cancers 3.1 versus 1.2 per 100 patient-years. CALGB 100104 (n=460, under 71): median time to progression 46 versus 27 months (P<0.001); deaths 15% versus 23% (P=0.03). Patient-level meta-analysis of three trials (n=1,208): median PFS 52.8 versus 23.5 months (HR 0.48); OS HR 0.75 (95% CI 0.63 to 0.90). FDA maintenance indication 22 February 2017.

  27. 2012 · Treatment · Multiple myeloma

    Carfilzomib: accelerated approval to ASPIRE and ENDEAVOR

    Carfilzomib is a proteasome inhibitor given by infusion. After a single-agent study in heavily treated myeloma, the US granted accelerated approval in 2012, pending confirmatory trials. Two randomised trials, one adding it to lenalidomide and dexamethasone and one comparing it with bortezomib, found longer time without progression; the single-agent approval was later made regular.

    PX-171-003-A1 (single-arm phase 2, 257 evaluable for efficacy): ORR 23.7%, median DOR 7.8 months, median OS 15.6 months. ASPIRE (KRd versus Rd, n=792): median PFS 26.3 versus 17.6 months, HR 0.69 (95% CI 0.57 to 0.83); 24-month OS 73.3% versus 65.0%. ENDEAVOR (Kd versus Vd, n=929): median PFS 18.7 versus 9.4 months, HR 0.53 (0.44 to 0.65). Interim analyses. FDA accelerated approval 2012; monotherapy converted 2016.

  28. 2012 · Treatment · Oesophageal cancer

    CROSS: neoadjuvant chemoradiotherapy for oesophageal cancer

    In a Dutch trial, people with cancer of the oesophagus or the junction with the stomach had either surgery alone or five weeks of chemotherapy with radiotherapy followed by surgery. Median survival was about 49 months with chemoradiotherapy and 24 months with surgery alone, and the survival gain was still present ten years later.

    CROSS (366 analysed; 75% adenocarcinoma, 23% squamous): weekly carboplatin and paclitaxel with 41.4 Gy, then surgery, versus surgery alone. R0 resection 92% vs 69%; median OS 49.4 vs 24.0 months (HR 0.657; 95% CI 0.495 to 0.871; P=0.003). Long-term: median OS 48.6 vs 24.0 months (HR 0.68); squamous HR 0.48, adenocarcinoma HR 0.73. Ten-year OS 38% vs 25% for chemoradiotherapy vs surgery alone (HR 0.70; 95% CI 0.55 to 0.89).

  29. 2012 · Treatment · Ovarian cancer

    Bevacizumab in recurrent disease: OCEANS, AURELIA, GOG-213

    Bevacizumab was added to chemotherapy in three randomised trials of recurrent ovarian cancer. It lengthened progression-free survival in platinum-sensitive disease (OCEANS) and platinum-resistant disease (AURELIA). In GOG-213, the survival difference in platinum-sensitive disease was not statistically significant in the main analysis.

    With vs without bevacizumab. OCEANS (N=484, platinum-sensitive, gemcitabine-carboplatin): median PFS 12.4 vs 8.4 months (HR 0.484; 95% CI 0.388-0.605). AURELIA (N=361, platinum-resistant): median PFS 6.7 vs 3.4 months (HR 0.48; 0.38-0.60); median OS 16.6 vs 13.3 months (HR 0.85; 0.66-1.08). GOG-213 (N=674, platinum-sensitive): median OS 42.2 vs 37.3 months (HR 0.829; 0.683-1.005; p=0.056).

  30. 2012 · Treatment · Ovarian cancer

    Olaparib maintenance in platinum-sensitive relapse: Study 19 and SOLO2

    Olaparib blocks PARP, an enzyme that helps cancer cells repair DNA. Taken after chemotherapy had controlled a returned ovarian cancer, it delayed progression: by about four months in Study 19, and by about fourteen months in SOLO2, which enrolled people with a BRCA mutation. The survival gains were not statistically significant.

    Study 19 (phase 2, N=265, serous, BRCA status not a selection criterion): median PFS 8.4 vs 4.8 months, HR 0.35 (95% CI 0.25-0.49); updated OS (77% maturity) HR 0.73 (0.55-0.96), nominal p=0.025, below the required threshold. SOLO2 (phase 3, BRCA1/2-mutated, N=295): investigator-assessed median PFS 19.1 vs 5.5 months, HR 0.30 (0.22-0.41); final OS 51.7 vs 38.8 months, HR 0.74 (0.54-1.00), p=0.054.

  31. 2012 · Detection · Pancreatic cancer

    Surveillance of high-risk individuals: CAPS studies and consensus

    From 2012, studies of people at high inherited risk of pancreatic cancer tested imaging surveillance. Of 216 evaluable people screened once, about four in ten had a pancreatic abnormality, mostly small cysts. Longer follow-up found cancers or high-grade precancerous changes in a minority. A consensus statement advised surveillance for selected people in research settings.

    Canto 2012: 225 asymptomatic high-risk individuals enrolled, 216 evaluable, screened once by CT, MRI and EUS; 92 of 216 (42%) had a mass or dilated duct (84 cystic, 3 solid). Canto 2018 (n=354, median follow-up 5.6 years): neoplastic progression in 24 (7%), 14 PDAC and 10 high-grade dysplasia. Overbeek 2022 (n=366): 10 PDAC. Goggins 2020: Delphi consensus on 55 statements.

  32. 2012 · Treatment · Prostate cancer

    Enzalutamide after docetaxel (AFFIRM)

    Enzalutamide, which blocks androgen-receptor signaling, was compared with placebo in 1,199 men whose castration-resistant prostate cancer had progressed after chemotherapy. Median survival was 18.4 months with enzalutamide and 13.6 months with placebo. The FDA approved enzalutamide on 31 August 2012.

    AFFIRM: randomized (2:1), double-blind, placebo-controlled phase 3, n=1199, castration-resistant prostate cancer after chemotherapy; enzalutamide 160 mg daily versus placebo. Stopped at a planned interim analysis (520 deaths): median OS 18.4 versus 13.6 months, HR 0.63 (95% CI 0.53-0.75; P<0.001); radiographic PFS 8.3 versus 2.9 months (HR 0.40). Seizures were reported in five patients (0.6%) given enzalutamide.

  33. 2012 · Detection · Prostate cancer

    USPSTF PSA screening recommendations (2012, 2018)

    In 2008 the US Preventive Services Task Force said the evidence was too thin to judge PSA screening for men under 75. In 2012 it recommended against PSA-based screening for all men in the general US population. In 2018 it changed this to an individual decision for ages 55 to 69, keeping the recommendation against screening from age 70.

    USPSTF 2008: insufficient evidence for men younger than 75 (I statement), against screening at 75 and older (grade D). 2012: against PSA-based screening for men in the general US population regardless of age (grade D). 2018: grade C for ages 55-69 (individual decision), grade D from 70. The 2018 statement estimates that screening men aged 55-69 may prevent about 1.3 prostate cancer deaths over about 13 years and about 3 metastatic cases per 1000 men screened.

  34. 2012 · Treatment · Sarcoma and GIST

    AEWS0031: interval-compressed chemotherapy in Ewing sarcoma

    A Children's Oncology Group trial compared giving the same Ewing sarcoma chemotherapy every two weeks or every three weeks. At five years, roughly three in four people given it every two weeks were free of events, against about two in three every three weeks. Side effects were reported as similar.

    AEWS0031: 587 enrolled, 568 eligible (284 per arm), age under 50, localized extradural Ewing sarcoma; vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide every 14 vs 21 days. 5-year EFS 73% vs 65% (HR 0.74, 95% CI 0.54-0.99; P=.048); toxicity similar. Update: 10-year EFS 70% vs 61% (P=.03), OS 76% vs 69% (P=.04); no difference in second malignant neoplasm incidence (P=.5).

  35. 2012 · Treatment · Sarcoma and GIST

    GRID: regorafenib after imatinib and sunitinib

    The GRID trial gave regorafenib or placebo to people with metastatic GIST that had progressed on imatinib and sunitinib. Median progression-free survival was 4.8 months with regorafenib and 0.9 months with placebo. The US regulator approved regorafenib for this use in February 2013.

    GRID, double-blind phase 3 (199 patients, 57 hospitals, 17 countries): regorafenib 160 mg daily (3 weeks of each 4; n=133) vs placebo (n=66), 2:1, plus best supportive care. Median PFS by independent central review 4.8 vs 0.9 months, HR 0.27 (95% CI 0.19-0.39), p<0.0001; 56 placebo patients (85%) crossed over. FDA approval 25 Feb 2013 under NDA 204369.

  36. 2012 · Treatment · Sarcoma and GIST

    PALETTE: pazopanib after chemotherapy in non-adipocytic sarcoma

    In 369 people with metastatic non-adipocytic soft-tissue sarcoma that had progressed after chemotherapy, the tablet pazopanib delayed progression compared with placebo: median 4.6 months versus 1.6 months. Overall survival was not significantly different (12.5 versus 10.7 months). Diarrhoea, nausea and high blood pressure were more common with pazopanib.

    Double-blind phase 3 (PALETTE; N=369, 2:1): pazopanib 800 mg daily (n=246) vs placebo (n=123), no crossover, after failure of standard chemotherapy. Median PFS (primary) 4.6 vs 1.6 months (HR 0.31; 95% CI 0.24-0.40; p<0.0001). Median OS 12.5 vs 10.7 months (HR 0.86; 95% CI 0.67-1.11; p=0.25). FDA approval 26 April 2012 for advanced STS after prior chemotherapy (limitation of use: adipocytic STS).

  37. 2012 · De-escalation · Thyroid cancer

    HiLo and ESTIMABL1: 1.1 GBq versus 3.7 GBq radioiodine ablation

    Two randomised trials compared a lower with a higher dose of radioactive iodine, given after surgery to destroy leftover thyroid tissue in low-risk thyroid cancer, with and without an injected hormone to prepare for treatment. The lower dose with the injection worked about as well. In the UK trial it brought fewer adverse events and fewer long hospital stays.

    HiLo (UK; n=438, 421 analysable): 1.1 vs 3.7 GBq radioiodine, each with thyrotropin alfa or hormone withdrawal. Ablation success at 6 to 9 months 85.0% vs 88.9% (low vs high dose) and 87.1% vs 86.7% (thyrotropin alfa vs withdrawal); 95% CIs for differences within 10 percentage points. Hospital stay of 3 days or more 13.0% vs 36.3% (low vs high dose). ESTIMABL1 (France; 752 enrolled): same 2-by-2 design; ablation complete in 631 of 684 evaluable patients (92%).

  38. 2012 · Treatment · Thyroid cancer

    EXAM and EXAMINER: cabozantinib in medullary thyroid cancer

    In EXAM, 330 people with medullary thyroid cancer that was getting worse took cabozantinib or placebo: those on cabozantinib went about 11 months before progression, against 4 months on placebo. The final survival analysis was not significantly different. A later trial did not show that a lower-dose tablet matched the capsule on progression-free survival.

    EXAM, phase 3, double-blind: 330 patients with radiographic progression of metastatic MTC randomised 2:1 to cabozantinib 140 mg/day or placebo. Median PFS 11.2 vs 4.0 months, HR 0.28 (95% CI 0.19-0.40), P<.001; ORR 28% vs 0%. Final OS: 26.6 vs 21.1 months, HR 0.85 (0.64-1.12), P=0.24. EXAMINER, phase 4 (247 patients; 60 mg tablet vs 140 mg capsule): median PFS 11.0 vs 13.9 months, HR 1.24 (0.90-1.70); non-inferiority not met.

  39. 2013 · Treatment · Acute myeloid leukaemia (including APL)

    APL0406: ATRA plus arsenic trioxide versus ATRA plus chemotherapy

    A trial of 276 adults with newly diagnosed, lower-risk acute promyelocytic leukemia compared retinoic acid plus arsenic trioxide with retinoic acid plus chemotherapy. At about four years, about 97 in 100 on arsenic had no event such as relapse or death, against about 80 in 100 on chemotherapy. The EU approved the combination in 2016, the US in 2018.

    APL0406: phase 3, open-label noninferiority trial in adults aged 18 to 71 with low- or intermediate-risk APL (WBC ≤10 × 10^9 per liter); ATRA plus arsenic trioxide versus ATRA plus idarubicin-based chemotherapy. Primary report: 2-year EFS 97% vs 86% (P<0.001 noninferiority, P=0.02 superiority). Final analysis, 276 randomized, median follow-up 40.6 months: 50-month EFS 97.3% vs 80%, cumulative incidence of relapse 1.9% vs 13.9%, OS 99.2% vs 92.6%.

  40. 2013 · Detection · Cervical cancer

    HPV testing versus cytology in screening: RCT follow-up and FDA 2014

    Four European trials had randomly assigned women to cervical screening based on HPV testing or on cytology (Pap tests). A pooled follow-up reported fewer invasive cervical cancers in the HPV-testing groups, mainly after the first two and a half years. In April 2014 the US FDA approved a test with first-line screening use for women aged 25 and older.

    Pooled follow-up of four RCTs (Swedescreen, POBASCAM, ARTISTIC, NTCC; 176,464 women aged 20-64; median follow-up 6.5 years; 107 invasive carcinomas). Rate ratio for invasive cervical carcinoma, HPV-based vs cytology-based screening: 0.60 (95% CI 0.40-0.89); 0.79 (0.46-1.36) in the first 2.5 years, 0.45 (0.25-0.81) thereafter; 0.30 (0.15-0.60) after a negative entry test. In April 2014 the FDA approved the cobas HPV Test for first-line screening at age 25 or older.

  41. 2013 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    CD19 CAR T cells induce remissions in children with relapsed ALL

    In 2013 doctors reported two children with relapsed leukemia who were given their own T cells, re-engineered to recognize CD19 on leukemia cells. Both reached remission. One stayed in remission for at least 11 months; in the other the leukemia returned about two months later without CD19. A 2014 report of 30 patients found remission in nine of ten.

    Grupp 2013: two children with relapsed, refractory pre-B-cell ALL given CTL019 CAR T cells; both reached complete remission, ongoing at 11 months in one, while the other relapsed about 2 months later with CD19-negative blasts. Maude 2014 (30 children and adults): complete remission 27 of 30 (90%); 6-month EFS 67% (95% CI 51 to 88), OS 78% (95% CI 65 to 95); severe cytokine-release syndrome in 27%.

  42. 2013 · De-escalation · Childhood acute lymphoblastic leukemia (ALL)

    MRD-guided treatment reduction for low-risk ALL (UKALL 2003)

    In the UK trial UKALL 2003, children and young adults whose leukemia cleared quickly were randomly given one or two courses of delayed intensification chemotherapy. Five-year event-free survival was 94.4 in 100 with one course and 95.5 in 100 with two, a difference that was not statistically significant.

    UKALL 2003 (UK and Ireland), ages 1 to 25 years: 3207 registered; 521 MRD low-risk patients randomised to one (260) or two (261) delayed intensifications; median follow-up 57 months. 5-year EFS 94.4% (95% CI 91.1-97.7) versus 95.5% (92.8-98.2); odds ratio 1.00 (0.43-2.31), P=0.99. Actuarial relapse 5.6% versus 2.4% (P=0.23). Treatment-related deaths: 3 with two courses (1.2%), none with one (P=0.08).

  43. 2013 · Understanding · Childhood acute lymphoblastic leukemia (ALL)

    Acute lymphoblastic leukemia in children with Down syndrome

    Children with Down syndrome have a higher risk of B-cell ALL. Two large analyses, one international and one from the Children's Oncology Group, found that they relapse more often and are more likely to die of treatment complications than other children, so survival is lower. Both called for less toxic treatment or better supportive care.

    Ponte di Legno (653 DS-ALL patients, 16 trials, 1995-2004) vs non-DS reference cohorts: 8-year EFS 64% vs 81%, OS 74% vs 89%, cumulative incidence of relapse 26% vs 15%, 2-year TRM 7% vs 2.0%. COG (743 DS vs 20,067 non-DS, ages 1-30, four B-ALL trials): 5-year EFS 79.2% vs 87.5%, OS 86.8% vs 93.6%; death in remission 4.9% vs 1.7%.

  44. 2013 · Treatment · Chronic lymphocytic leukaemia

    Ibrutinib: BTK inhibition for relapsed CLL, approved in 2014

    Ibrutinib is an oral medicine, taken once daily, that blocks BTK, a protein CLL cells rely on. In 2013 a study of 85 people with relapsed disease reported high response rates. In 2014 a randomised trial found people stayed free of progression longer than on an antibody drug, and the US regulator approved ibrutinib for relapsed CLL.

    Phase 1b-2 (n=85, single arm): ORR 71% at 420 mg and at 840 mg; estimated 26-month PFS 75%, OS 83%. RESONATE (phase 3, n=391, ibrutinib vs ofatumumab, relapsed/refractory CLL/SLL): median follow-up 9.4 months; PFS HR 0.22 (P<0.001), median 8.1 months with ofatumumab, not reached with ibrutinib; OS HR 0.43 (P=0.005); ORR 42.6% vs 4.1%. FDA accelerated approval 12 February 2014; accelerated-approval requirements fulfilled 28 July 2014.

  45. 2013 · Treatment · Chronic lymphocytic leukaemia

    CLL11: anti-CD20 plus chlorambucil in patients with comorbidities

    In people with untreated CLL and other health conditions, adding an antibody to the tablet chemotherapy chlorambucil delayed progression. In a three-arm trial of 781 people, median time without progression was about 27 months with obinutuzumab, 16 months with rituximab and 11 months with chlorambucil alone.

    CLL11 (NCT01010061): three-arm open-label phase 3, 781 randomised, untreated CLL with CIRS >6 or creatinine clearance 30-69 ml/min; primary endpoint investigator-assessed PFS. Median PFS 26.7 months with obinutuzumab-chlorambucil, 16.3 with rituximab-chlorambucil, 11.1 with chlorambucil; HR 0.18 (95% CI 0.13-0.24) and 0.44 (0.34-0.57). Obinutuzumab vs rituximab HR 0.39 (0.31-0.49). OS vs chlorambucil HR 0.41 (0.23-0.74). FDA approval 1 November 2013.

  46. 2013 · Reversal · Chronic myeloid leukemia

    Ponatinib marketing suspended over arterial occlusive events

    In October 2013 the maker of ponatinib voluntarily suspended US marketing after reports and trial data pointed to more serious blood-vessel blockages. On 20 December 2013 the US regulator approved new warnings and a risk-management programme, and said the suspension would no longer be warranted once that programme was fully operational.

    FDA letter of 20 December 2013 (S-007 and S-008) acknowledges the sponsor's voluntary suspension of marketing from 31 October 2013 after postmarketing reports and trial follow-up data showing an increased frequency of serious vascular occlusive events, approves revised labeling and a REMS, and requires postmarketing studies. PACE reported serious arterial thrombotic events in 9% of patients (3% treatment-related); at final analysis cumulative arterial occlusive events were 31% in chronic phase.

  47. 2013 · Understanding · Endometrial cancer

    TCGA: four molecular groups of endometrial carcinoma

    In 2013 researchers studied the genes of 373 endometrial cancers and sorted them into four groups by their DNA changes. Serous tumours resembled some ovarian and breast cancers. The authors suggested that this could change which women with aggressive tumours receive further treatment after surgery.

    Integrated genomic, transcriptomic and proteomic study of 373 endometrial carcinomas. Four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low and copy-number high. Uterine serous tumours and about 25% of high-grade endometrioid tumours had extensive copy-number alterations, few methylation changes and frequent TP53 mutations. The authors reported that the genomic features permit a reclassification that may affect adjuvant treatment of women with aggressive tumours.

  48. 2013 · Treatment · Gastric and gastro-oesophageal junction cancer

    REGARD and RAINBOW: ramucirumab after first-line therapy

    In 2013 and 2014 two placebo-controlled trials tested ramucirumab, an antibody that blocks a blood-vessel growth receptor, in advanced stomach or junction cancer that had progressed on first-line chemotherapy. Alone it lengthened median survival modestly, from 3.8 to 5.2 months; with paclitaxel it added about two months, from 7.4 to 9.6 months.

    REGARD (355 patients, 2:1, best supportive care with ramucirumab 8 mg/kg or placebo): median OS 5.2 vs 3.8 months, HR 0.776 (95% CI 0.603 to 0.998), p=0.047. RAINBOW (665 patients, 1:1, paclitaxel with ramucirumab or placebo): median OS 9.6 vs 7.4 months, HR 0.807 (0.678 to 0.962), p=0.017. Hypertension was more frequent with ramucirumab in both trials.

  49. 2013 · Reversal · Glioblastoma

    Dose-dense temozolomide shows no survival gain (RTOG 0525)

    A 2013 trial of 833 people with newly diagnosed glioblastoma compared standard temozolomide with a dose-dense schedule after chemoradiation. Median survival was about 17 months with the standard schedule and 15 months with the dose-dense schedule, not a significant difference. Severe side effects were more common with the dose-dense schedule.

    RTOG 0525 (833 randomised of 1,173 registered): standard vs dose-dense temozolomide, median OS 16.6 vs 14.9 months (HR 1.03; P=.63); median PFS 5.5 vs 6.7 months (HR 0.87; P=.06). Treatment effect did not differ by MGMT methylation status. Across both arms, MGMT methylation was associated with better OS (21.2 vs 14 months; HR 1.74 as printed, between methylation groups; P<.001). Grade 3 or higher toxicity 34% vs 53% (P<.001).

  50. 2013 · Reversal · Non-Hodgkin lymphoma (DLBCL and follicular)

    R-CHOP-14 not better than R-CHOP-21 (two randomised trials, 2013)

    Two large randomised trials asked whether giving R-CHOP every two weeks instead of every three helps. A trial in 602 people aged 60 to 80 and a UK trial in 1,080 adults found no survival gain from the two-week schedule. In the UK trial, 2-year survival was 83 in 100 versus 81 in 100.

    Two separate randomised phase 3 trials, not pooled. LNH03-6B (602 patients aged 60-80, aaIPI 1 or more): 3-year EFS 56% (R-CHOP-14) vs 60% (R-CHOP-21), HR 1.04 (95% CI 0.82-1.31; P=0.7614); red-cell transfusion 47% vs 31%. UK trial (1080 adults): 2-year OS 82.7% vs 80.8%, HR 0.90 (0.70-1.15; P=0.3763); 2-year PFS 75.4% vs 74.8% (HR 0.94, 0.76-1.17).

  51. 2013 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    StiL: bendamustine-rituximab vs R-CHOP, first-line indolent/MCL

    In a German trial of people with newly diagnosed advanced indolent or mantle-cell lymphoma, median progression-free survival was about 70 months with bendamustine plus rituximab versus about 31 months with R-CHOP, with less hair loss, nerve damage and low blood counts. The trial mixed several lymphoma types.

    Open-label phase 3 non-inferiority (n=549), untreated stage III or IV indolent or mantle-cell lymphoma, bendamustine-rituximab versus R-CHOP; per-protocol analysis, median follow-up 45 months. Median PFS 69.5 versus 31.2 months (HR 0.58, 95% CI 0.44 to 0.74; p<0.0001). Peripheral neuropathy 7% versus 29%. BRIGHT (n=447): 5-year PFS 65.5% versus 55.8% (HR 0.61, 95% CI 0.45 to 0.85).

  52. 2013 · Treatment · Multiple myeloma

    Treating smouldering myeloma: from lenalidomide to daratumumab

    Smouldering myeloma is an early stage without symptoms, usually managed by watching. Three randomised trials compared early treatment with watching: lenalidomide-based treatment (reported in 2013 and 2019) and daratumumab (2024). Each reported a longer time before the disease progressed with treatment. In November 2025 the US regulator approved daratumumab for adults with high-risk smouldering myeloma.

    Three randomised trials, each reported separately. QuiRedex (n = 119; lenalidomide-dexamethasone vs observation): TTP HR 0.18 (95% CI 0.09-0.32). E3A06 (n = 182; lenalidomide vs observation): PFS HR 0.28 (0.12-0.62). AQUILA (n = 390; SC daratumumab vs active monitoring): PFS HR 0.49 (0.36-0.67), 5-year PFS 63.1% vs 40.8%, OS HR 0.52 (0.27-0.98). FDA approved daratumumab monotherapy for high-risk smouldering myeloma on 6 November 2025.

  53. 2013 · Treatment · Pancreatic cancer

    MPACT: nab-paclitaxel plus gemcitabine improves survival

    In 861 people with spread pancreatic cancer, adding nab-paclitaxel to gemcitabine lengthened median survival from about 6.7 to about 8.5 months. Nerve damage and low blood counts were more common. The US regulator approved the combination in September 2013.

    MPACT, phase 3: 861 patients with metastatic pancreatic cancer, KPS 70 or more; nab-paclitaxel plus gemcitabine vs gemcitabine. Median OS 8.5 vs 6.7 months, HR 0.72 (95% CI 0.62-0.83; P<0.001); 1-year survival 35% vs 22%. PFS 5.5 vs 3.7 months (HR 0.69). Grade 3 or higher neuropathy 17% vs 1%. Post hoc update: median OS 8.7 vs 6.6 months.

  54. 2013 · Treatment · Prostate cancer

    Radium-223 and survival in bone-metastatic CRPC (ALSYMPCA)

    Radium-223 is a radioactive drug that gives off alpha particles and targets bone metastases. In ALSYMPCA, men with castration-resistant prostate cancer and bone metastases who received it lived longer than those given placebo: about 15 months versus 11 months in the updated analysis, with low rates of bone-marrow suppression.

    Phase 3, double-blind trial (N=921) in castration-resistant prostate cancer with bone metastases: radium-223 (50 kBq/kg, six 4-weekly injections) versus placebo, 2:1, plus best standard of care. Primary endpoint OS. Interim analysis (809 patients): median 14.0 vs 11.2 months, HR 0.70 (95% CI 0.55-0.88; P=0.002). Updated analysis (528 deaths, before crossover): 14.9 vs 11.3 months, HR 0.70 (0.58-0.83; P<0.001).

  55. 2013 · Treatment · Thyroid cancer

    DECISION: sorafenib for radioiodine-refractory thyroid cancer

    In people whose thyroid cancer had stopped responding to radioactive iodine and was growing, sorafenib was compared with placebo. The median time before the cancer grew was about 11 months with sorafenib and about 6 with placebo. Hand and foot skin reactions, diarrhoea and hair loss were common. The FDA approved it in November 2013, before the trial report appeared.

    DECISION (n=417), double-blind phase 3: sorafenib 400 mg twice daily (n=207) vs placebo (n=210) in radioactive iodine-refractory locally advanced or metastatic DTC that progressed within 14 months. Median PFS by central independent review 10.8 vs 5.8 months (HR 0.59; 95% CI 0.45 to 0.76; p<0.0001), consistent across prespecified subgroups. Hand-foot skin reaction 76.3%, diarrhoea 68.6%, alopecia 67.1% with sorafenib.

  56. 2014 · Treatment · Cervical cancer

    GOG-240: bevacizumab added to chemotherapy (FDA 2014)

    In 452 people whose cervical cancer had spread, persisted or returned, adding the antibody bevacizumab to chemotherapy was linked to median survival of about 17 months instead of about 13. High blood pressure, blood clots and abnormal channels between organs (fistulas) were more common with bevacizumab.

    Phase 3, open-label, factorial design (N=452): chemotherapy (cisplatin or topotecan, plus paclitaxel) with or without bevacizumab. Combined regimens, second interim analysis: median OS 17.0 vs 13.3 months (HR 0.71; 98% CI 0.54-0.95). Final analysis: 16.8 vs 13.3 months (HR 0.77; 95% CI 0.62-0.95). Topotecan-paclitaxel versus cisplatin-paclitaxel: median OS 13.8 vs 16.3 months (HR 1.12). Final analysis, grade 3 fistula 6% vs <1%.

  57. 2014 · Reversal · Glioblastoma

    Bevacizumab added to chemoradiation does not improve survival

    In 2014 two large randomised trials added bevacizumab to radiotherapy and temozolomide for newly diagnosed glioblastoma. People given bevacizumab went longer before their tumour progressed, but overall survival was not significantly different, and more had severe side effects.

    AVAglio (458 bevacizumab, 463 placebo): median PFS 10.6 vs 6.2 months, stratified HR 0.64 (95% CI 0.55 to 0.74); OS stratified HR 0.88 (95% CI 0.76 to 1.02; P=0.10); grade 3 or higher adverse events 66.8% vs 51.3%. RTOG 0825 (n=637 randomised): median OS 15.7 vs 16.1 months (HR 1.13); PFS 10.7 vs 7.3 months (HR 0.79), below the prespecified target.

  58. 2014 · Reversal · Glioblastoma

    Three further add-on agents fail in randomised phase 3 trials

    Three randomised phase 3 trials added a new drug to radiotherapy and temozolomide in newly diagnosed glioblastoma: cilengitide (reported 2014), a vaccine called rindopepimut (2017) and marizomib (2024). None improved overall survival, and the cilengitide authors said it would not be developed further.

    CENTRIC (MGMT-methylated, n=545): median OS 26.3 vs 26.3 months, HR 1.02 (95% CI 0.81 to 1.29; P=0.86). ACT IV (EGFRvIII-expressing; 745 enrolled; minimal residual disease group): median OS 20.1 vs 20.0 months, HR 1.01 (95% CI 0.79 to 1.30); terminated for futility at interim. EORTC 1709 marizomib (n=749): median OS 17 months with standard treatment vs 16.5 with marizomib, HR 1.04 (P=.64); more grade 3 or 4 adverse events with marizomib.

  59. 2014 · Treatment · Hodgkin lymphoma

    PD-1 blockade for relapsed Hodgkin lymphoma

    In heavily treated people whose Hodgkin lymphoma had come back, antibodies that block the PD-1 immune checkpoint shrank the cancer in about two in three people in the larger studies, and in 87 in 100 in the first small study of 23. These were single-group studies with no comparison arm.

    Single-arm studies in relapsed or refractory classic HL. Nivolumab first report (n=23): ORR 87%. CheckMate 205 (n=243, median follow-up 18 months): ORR 69% (95% CI 63 to 75), median DOR 16.6 months, median PFS 14.7 months. KEYNOTE-087, pembrolizumab (n=210): ORR 69.0% (95% CI 62.3 to 75.2), complete response 22.4%. FDA accelerated approvals: nivolumab 17 May 2016, pembrolizumab 14 March 2017.

  60. 2014 · De-escalation · Hodgkin lymphoma

    EORTC H10: PET-guided omission of radiotherapy tested

    In EORTC H10, people with early-stage Hodgkin lymphoma had a PET scan after two cycles of ABVD. A planned interim analysis found more early progressions when radiotherapy was left out after a negative scan, and the monitoring committee advised stopping randomisation to omission. The final report could not show that ABVD alone was no worse.

    EORTC/LYSA/FIL H10. Interim (Raemaekers 2014, 1,137 analysed): early PET negative in 85.8% (favourable) and 74.8% (unfavourable); events, standard vs experimental: favourable 1 vs 9, unfavourable 7 vs 16; committee advised stopping random assignment. Final (André 2017, 1950 randomised): ePET-negative 5-year PFS, ABVD + INRT vs ABVD only, 99.0% vs 87.1% (favourable; HR 15.8) and 92.1% vs 89.6% (unfavourable; HR 1.45); noninferiority not shown.

  61. 2014 · Treatment · Lung cancer

    ROS1-positive NSCLC: crizotinib to taletrectinib

    ROS1 rearrangements define a small group of lung cancers. In 2014 crizotinib shrank tumours in about seven in ten of 50 people in a single-arm cohort. Entrectinib, repotrectinib and taletrectinib followed, each reported in single-arm studies with response rates of roughly three-quarters to nine in ten in people not previously given a ROS1 inhibitor.

    Single-arm cohorts in ROS1-positive NSCLC. Crizotinib (n=50): ORR 72% (95% CI 58-84), median PFS 19.2 months. Entrectinib integrated analysis (n=53): ORR 77% (64-88), median DOR 24.6 months. Repotrectinib, no previous ROS1 TKI (n=71): ORR 79% (68-88), median PFS 35.7 months; one previous TKI (n=56): ORR 38%, PFS 9.0 months. Taletrectinib pooled, TKI-naive (n=160): ORR 88.8%, median PFS 45.6 months.

  62. 2014 · Treatment · Melanoma

    Dabrafenib plus trametinib: COMBI-d and COMBI-v (2014)

    Two large trials added a MEK inhibitor, trametinib, to a BRAF inhibitor in melanoma with a BRAF mutation. The combination delayed progression compared with dabrafenib alone and was linked to longer survival than dabrafenib alone or vemurafenib. The FDA had approved the combination in January 2014, before either trial appeared in a journal.

    COMBI-d (n=423, untreated BRAF V600E/K): dabrafenib plus trametinib vs dabrafenib plus placebo, median PFS 9.3 vs 8.8 months (HR 0.75; 95% CI 0.57 to 0.99); OS in the Lancet report 25.1 vs 18.7 months (HR 0.71; 95% CI 0.55 to 0.92). COMBI-v (n=704): vs vemurafenib, 12-month OS 72% vs 65% (HR 0.69; 95% CI 0.53 to 0.89; P=0.005). Pooled five-year OS 34%.

  63. 2014 · Treatment · Melanoma

    Nivolumab monotherapy: CheckMate 066 and CheckMate 037 (2014-2015)

    Two trials tested nivolumab against chemotherapy. In untreated melanoma without a BRAF mutation, people on nivolumab were more likely to be alive at one year and had more responses than those on dacarbazine. After ipilimumab, nivolumab produced more responses than chemotherapy at an interim analysis. The two groups are different populations.

    CheckMate 066 (n=418, untreated, BRAF wild-type): nivolumab vs dacarbazine, 1-year OS 72.9% vs 42.1% (HR 0.42; 99.79% CI 0.25 to 0.73); median PFS 5.1 vs 2.2 months (HR 0.43); response 40.0% vs 13.9%. CheckMate 037 (n=405, after ipilimumab): response 31.7% vs 10.6% in the first interim analysis.

  64. 2014 · Treatment · Multiple myeloma

    FIRST and SWOG S0777: lenalidomide-based first-line treatment

    Two trials in newly diagnosed myeloma without immediate transplant tested lenalidomide-based treatment. In FIRST, continuous lenalidomide with dexamethasone gave longer progression-free survival than melphalan, prednisone and thalidomide. In SWOG S0777, adding bortezomib to lenalidomide and dexamethasone gave longer progression-free and overall survival. Each trial has its own comparison.

    FIRST (n=1623): continuous lenalidomide-dexamethasone versus MPT, median PFS 25.5 versus 21.2 months (HR 0.72; P<0.001); final analysis median OS 59.1 versus 49.1 months (HR 0.78; 95% CI 0.67 to 0.92). SWOG S0777 (n=525): VRd versus Rd, median PFS 43 versus 30 months (HR 0.712, 96% CI 0.56 to 0.906), median OS 75 versus 64 months (HR 0.709; 95% CI 0.524 to 0.959).

  65. 2014 · Understanding · Multiple myeloma

    IMWG 2014 criteria: biomarkers join CRAB to define myeloma

    In 2014 an international expert group changed the definition of myeloma. Besides organ damage, three laboratory or imaging markers could now identify people very likely to develop that damage, so they could be called myeloma, and offered treatment, earlier. Some people previously labelled smouldering myeloma were reclassified.

    IMWG consensus (Rajkumar 2014) added validated biomarkers to the CRAB features (hypercalcaemia, renal failure, anaemia, bone lesions) in the myeloma definition, for patients otherwise classed as smouldering. A 2023 meta-analysis (Ludwig) describes them as ≥60% bone marrow plasma cells, free light chain ratio ≥100 and >1 MRI focal lesion of ≥5 mm. No trial data are reported in the consensus.

  66. 2014 · Treatment · Sarcoma and GIST

    EORTC 62012: doxorubicin vs doxorubicin plus ifosfamide

    In 455 adults aged 18 to 60 with advanced soft-tissue sarcoma, adding ifosfamide to doxorubicin (given on an intensified schedule) did not significantly lengthen overall survival (median 14.3 versus 12.8 months). It lengthened progression-free survival (7.4 versus 4.6 months) and tumours responded more often (26% versus 14%), with more blood-count toxicity.

    Phase 3 (EORTC 62012; N=455; age 18-60, WHO PS 0-1, high-grade): doxorubicin 75 mg/m2 (n=228) vs intensified doxorubicin plus ifosfamide 10 g/m2 with pegfilgrastim (n=227), up to six cycles. Median OS (primary, ITT) 12.8 vs 14.3 months (HR 0.83; 95.5% CI 0.67-1.03; p=0.076). Median PFS 4.6 vs 7.4 months (HR 0.74; 95% CI 0.60-0.90; p=0.003). Response 14% vs 26%. Febrile neutropenia 13% vs 46%.

  67. 2014 · Treatment · Testicular germ cell tumors

    GETUG 13: tumour-marker decline guides dose-dense chemotherapy

    After one cycle of BEP in poor-prognosis non-seminoma, patients whose tumour markers fell too slowly were randomised to continue BEP or switch to a dose-dense regimen. Three-year progression-free survival was about 59 in 100 versus 48 in 100; at a median of seven years, five-year overall survival was 71% versus 61%, not statistically significant.

    GETUG 13, phase 3, 263 patients with IGCCCG poor-prognosis NSGCT; after 1 cycle of BEP, 203 with unfavourable marker decline randomised to BEP or dose-dense chemotherapy (paclitaxel-BEP-oxaliplatin, then cisplatin-ifosfamide-bleomycin). 3-year PFS 59% vs 48% (HR 0.66; 95% CI 0.44-1.00; P = 0.05). Update, median 7.1 years: 5-year PFS 58.9% vs 46.7% (HR 0.65; 0.44-0.97; P = 0.036); OS 70.9% vs 61.3% (HR 0.74; 0.46-1.20; P = 0.22).

  68. 2014 · Understanding · Thyroid cancer

    Thyroid incidence up, mortality flat: the overdiagnosis argument

    From 1975 to 2009 the rate of new thyroid cancers in nine US registry areas nearly tripled, almost all of it papillary cancers, while the death rate stayed flat. The authors of the 2014 report argue that this reflects more cancers being found, not more people becoming ill.

    Davies and Welch 2014 (JAMA Otolaryngol Head Neck Surg), SEER 9, adults, 1975 to 2009: incidence 4.9 to 14.3 per 100,000 (relative rate 2.9, 95% CI 2.7-3.1); papillary 3.4 to 12.5 (3.7, 3.4-4.0); women 6.5 to 21.4, men 3.1 to 6.9; mortality stable at about 0.5 per 100,000. Overdiagnosis is the authors' interpretation of registry trends, not a registry finding. SEER Stat Facts: 13.7 per 100,000 (2019-2023).

  69. 2015 · Treatment · Breast cancer

    CDK4/6 inhibitors added to first-line endocrine therapy

    In 2015 the US regulator gave palbociclib accelerated approval with letrozole as initial therapy for advanced hormone-receptor-positive breast cancer. Phase 3 trials in 2016 and 2017 then tested three CDK4/6 inhibitors with an aromatase inhibitor, each delaying progression; with palbociclib, median progression-free survival was 24.8 versus 14.5 months. Longer follow-up showed a survival gain with ribociclib.

    Phase 3, first-line, postmenopausal HR-positive, HER2-negative advanced disease. PALOMA-2 (N=666): median PFS 24.8 vs 14.5 months, HR 0.58 (0.46-0.72). MONALEESA-2 (N=668): PFS HR 0.56 (0.43-0.72); final OS 63.9 vs 51.4 months, HR 0.76 (0.63-0.93). MONARCH 3 (N=493): PFS HR 0.54 (0.41-0.72); final OS HR 0.804 (0.637-1.015), not significant.

  70. 2015 · De-escalation · Breast cancer

    PRIME II: omitting radiotherapy in low-risk older women

    PRIME II asked whether older women with small, low-risk, hormone-sensitive breast cancers who had breast-conserving surgery and endocrine treatment could skip radiotherapy. Without radiotherapy, local recurrence was higher. At ten years, survival was almost identical and distant spread was not higher.

    PRIME II (1,326 women aged 65 or older; hormone receptor-positive, node-negative, T1-T2 up to 3 cm, clear margins; breast-conserving surgery plus endocrine therapy): whole-breast radiotherapy vs none. 5-year IBTR 1.3% vs 4.1% (HR 5.19, 95% CI 1.99-13.52). 10-year local recurrence 0.9% vs 9.5% (HR 10.4, 95% CI 4.1-26.1; P<0.001); distant recurrence as first event 3.0% vs 1.6%; overall survival 80.7% vs 80.8%.

  71. 2015 · Treatment · Chronic lymphocytic leukaemia

    Venetoclax: BCL2 inhibition, from phase 1 to MURANO

    Venetoclax blocks BCL2, a protein that helps leukemia cells survive. A phase 1 study in people, reported in 2015, found responses in most people with relapsed CLL. In MURANO, two years of venetoclax with six months of rituximab left about 85% free of progression at two years, versus about 36% with bendamustine plus rituximab.

    Phase 1 (116 patients with relapsed or refractory CLL or SLL): response 79%, complete remission 20%. Single-arm phase 2, del(17p) CLL (107 patients): response 79.4% (95% CI 70.5 to 86.6). MURANO (389 randomised): venetoclax-rituximab vs bendamustine-rituximab, 24-month investigator-assessed PFS 84.9% vs 36.3% (HR 0.17, 95% CI 0.11 to 0.25; P<0.001). Final analysis: median PFS 54.7 vs 17.0 months; 7-year OS 69.6% vs 51.0%.

  72. 2015 · Treatment · Chronic lymphocytic leukaemia

    Ibrutinib as first-line therapy: RESONATE-2, A041202, E1912

    Ibrutinib was tested as first treatment for CLL in four randomised trials, against chlorambucil, bendamustine-rituximab and fludarabine-based chemoimmunotherapy. In each trial, ibrutinib treatment delayed progression for longer than its own comparator did. The US regulator approved ibrutinib for first-line CLL in 2016.

    RESONATE-2 (n=269, age 65 or older): median PFS not reached vs 18.9 months with chlorambucil, HR 0.16. A041202 (n=547): 2-year PFS 87% ibrutinib and 88% ibrutinib-rituximab vs 74% BR (HR 0.39 and 0.38). E1912 (n=529, 70 or younger): 3-year PFS 89.4% vs 72.9% with FCR, HR 0.35. FLAIR (n=771, interim): PFS HR 0.44 vs FCR. Different controls; not pooled.

  73. 2015 · Understanding · Chronic myeloid leukemia

    Life expectancy in CML approaches that of the general population

    Two analyses from the TKI era found that survival with CML has come close to that of the general population. In an MD Anderson cohort of 483 trial participants with chronic-phase CML, five-year survival was about 95% of that of a matched general population. In Sweden, people diagnosed in 2013 were predicted to lose fewer than three years of life.

    Sasaki 2015: 483 patients with newly diagnosed CML-CP in six consecutive TKI trials at one institution (2000-2012): 5-year relative survival 94.7% (95% CI 92.1-97.4) against a matched general population. Bower 2016: Swedish Cancer Registry, 2,662 patients diagnosed 1973-2013; modelled life-years lost to CML for patients of all ages diagnosed in 2013 <3. Different designs; figures are not combined.

  74. 2015 · Treatment · Colorectal cancer

    PD-1 blockade in mismatch repair-deficient colorectal cancer

    Tumours that cannot repair DNA copying errors carry many mutations. In a small 2015 study, pembrolizumab produced responses in 4 of 10 such bowel cancers and in none of 18 without the repair defect. Later nivolumab studies, with and without ipilimumab, reported responses in about a third to over half of previously treated patients, all without a comparison group.

    Non-randomised phase 2 studies. Le 2015 (n=41 across cohorts): immune-related ORR 40% (4 of 10) in dMMR colorectal vs 0% (0 of 18) in pMMR. CheckMate 142, previously treated: nivolumab ORR 31.1% (95% CI 20.8 to 42.9; n=74); nivolumab plus ipilimumab 55% (45.2 to 63.8; n=119). First line, nivolumab plus low-dose ipilimumab: 69% (53 to 82; n=45). FDA accelerated approvals 31 July 2017 and 10 July 2018.

  75. 2015 · Treatment · Colorectal cancer

    Trifluridine-tipiracil (TAS-102): RECOURSE and SUNLIGHT

    Trifluridine-tipiracil is an oral chemotherapy tablet. In a placebo-controlled trial of refractory metastatic bowel cancer it lengthened survival by under two months. A later trial in a similar setting found that adding bevacizumab to it lengthened survival by about three months compared with the tablet alone.

    RECOURSE (double-blind phase 3, n=800, 2:1): median OS 7.1 months with trifluridine-tipiracil vs 5.3 with placebo (HR 0.68, 95% CI 0.58-0.81; P<0.001). SUNLIGHT (open-label phase 3, 246 per arm, at most two prior regimens): trifluridine-tipiracil plus bevacizumab vs trifluridine-tipiracil alone, median OS 10.8 vs 7.5 months (HR 0.61, 95% CI 0.49-0.77); median PFS 5.6 vs 2.4 months (HR 0.44, 95% CI 0.36-0.54).

  76. 2015 · Understanding · Endometrial cancer

    ProMisE and PORTEC-3: molecular classes in high-risk disease

    In 2015 researchers showed that the four genomic groups of endometrial cancer could be approximated with three routine tests on stored tissue. When the tests were applied to PORTEC-3 tissue in 2020, outcomes differed widely between groups, and the apparent benefit of added chemotherapy was clearest in one group, the p53-abnormal tumours.

    ProMisE (2015): surrogate for the TCGA classes using mismatch repair immunohistochemistry, POLE mutation analysis and p53 immunohistochemistry; tested in an independent cohort of 152 cases and confirmed in 319 further samples (2017). PORTEC-3 tissue (410 classified): 5-year RFS 48% (p53abn), 98% (POLEmut), 72% (MMRd), 74% (NSMP). Subgroup 5-year RFS, chemoradiotherapy vs radiotherapy: p53abn 59% vs 36% (p=0.019); other classes no significant difference.

  77. 2015 · Understanding · Glioblastoma

    IDH, 1p/19q and TERT define diffuse glioma groups

    Two 2015 studies showed that a few DNA features, IDH mutation, 1p/19q loss and TERT mutation, sort diffuse gliomas into groups that differ in age at diagnosis and outcome. Most lower-grade gliomas without an IDH mutation resembled glioblastoma.

    TCGA: 293 adult grade II and III gliomas; three prognostic classes captured better by IDH, 1p/19q and TP53 status than by histology; IDH-mutant with 1p/19q codeletion had the most favourable outcomes; most IDH-wildtype lower-grade gliomas resembled primary glioblastoma. Eckel-Passow: 1087 gliomas scored for TERT promoter, IDH and 1p/19q: five groups; among 472 grade IV gliomas 74% had only TERT mutation and 7% only IDH; groups were associated with overall survival in grade II and III but not grade IV.

  78. 2015 · Treatment · Glioblastoma

    Tumour treating fields added to maintenance temozolomide (EF-14)

    In 2015 FDA approved a device that delivers electric fields through the scalp (tumour treating fields) for newly diagnosed glioblastoma. The open-label EF-14 trial, which enrolled people only after chemoradiation, reported median overall survival of about 21 months with the device plus temozolomide and 16 months with temozolomide alone. Its place in care is debated.

    EF-14 (695 randomised 2:1 after chemoradiation, open-label): TTFields plus maintenance temozolomide vs temozolomide alone. Final analysis (ITT): median PFS 6.7 vs 4.0 months (HR 0.63; 95% CI 0.52-0.76; P<.001); median OS 20.9 vs 16.0 months (HR 0.63; 0.53-0.76; P<.001). Skin toxicity under the arrays in 52% vs none. Randomised after a median 3.8 months from diagnosis.

  79. 2015 · Treatment · Head and neck cancer

    Elective vs therapeutic neck dissection in early oral cancer (Tata)

    In early oral cancer with no sign of spread to the neck, 500 patients were included in a prespecified report comparing removal of the neck lymph nodes during the first operation with waiting and operating only if cancer appeared in the neck. At three years, survival was about 80 percent with early neck surgery and about 68 percent with waiting.

    Tata Memorial randomised trial, lateralised T1-T2 oral squamous-cell carcinoma; prespecified report of the first 500 of 596 patients (245 elective, 255 therapeutic neck dissection), median follow-up 39 months. 3-year OS 80.0% (95% CI 74.1-85.8) vs 67.5% (61.0-73.9); HR for death 0.64 (95% CI 0.45-0.92; P=0.01). 3-year DFS 69.5% vs 45.9% (P<0.001). Adverse events 6.6% vs 3.6%.

  80. 2015 · Reversal · Hepatocellular carcinoma

    STORM: adjuvant sorafenib did not improve recurrence-free survival

    After surgery or local ablation for liver cancer, 1,114 people were randomly assigned to sorafenib tablets or a placebo for up to four years to see whether it delayed recurrence. Median recurrence-free survival was about 33 months in both groups, and the authors concluded that sorafenib was not effective in this setting.

    Phase 3, double-blind, placebo-controlled trial, N=1114 with a complete radiological response after resection or ablation: sorafenib 400 mg twice daily vs placebo for up to 4 years. Final analysis (464 events): median RFS 33.3 vs 33.7 months (HR 0.940; 95% CI 0.780-1.134; one-sided p=0.26). Grade 3 or 4 hand-foot skin reaction: 28% vs <1%.

  81. 2015 · Treatment · Hodgkin lymphoma

    AETHERA: brentuximab vedotin consolidation after ASCT

    After a stem-cell transplant for Hodgkin lymphoma that had returned or not responded to first treatment, people at higher risk of further progression were given brentuximab vedotin or placebo for up to 16 cycles. The brentuximab group stayed free of progression longer: a median of about 43 months compared with 24 months.

    Double-blind phase 3 (329 randomised), unfavourable-risk relapsed or primary refractory classic HL after ASCT: brentuximab vedotin 1.8 mg/kg or placebo every 3 weeks for 16 cycles. PFS by independent review: HR 0.57 (95% CI 0.40 to 0.81; P=0.0013); median 42.9 versus 24.1 months. Peripheral sensory neuropathy 56% versus 16%.

  82. 2015 · De-escalation · Hodgkin lymphoma

    RAPID: omitting radiotherapy after a negative PET

    In the RAPID trial, people with early-stage Hodgkin lymphoma and a negative PET scan after three cycles of ABVD were randomly given radiotherapy or no further treatment. About ninety-five in a hundred were alive without progression at three years with radiotherapy and about ninety-one without. The trial did not show that stopping was no worse.

    RAPID (Radford 2015): 602 patients with stage IA/IIA HL received 3 cycles of ABVD; 426 of 571 scanned (74.6%) were PET-negative, and 420 were randomised to involved-field radiotherapy (n=209) or no further therapy (n=211). Median follow-up 60 months. 3-year PFS 94.6% (95% CI 91.5-97.7) vs 90.8% (86.9-94.8); difference -3.8 percentage points (95% CI -8.8 to 1.3), margin 7 points. Noninferiority not shown.

  83. 2015 · Treatment · Kidney cancer (renal cell carcinoma)

    CheckMate 025: nivolumab versus everolimus in treated RCC (2015)

    In people whose kidney cancer had progressed after one or two antiangiogenic treatments, nivolumab was compared with everolimus. Median survival was about five months longer with nivolumab, and more tumours shrank. Progression-free survival was similar. The FDA approved nivolumab for this use in November 2015.

    CheckMate 025 (phase 3, n=821, clear-cell RCC after 1-2 antiangiogenic regimens): nivolumab 3 mg/kg every 2 weeks vs everolimus 10 mg daily. Median OS 25.0 vs 19.6 months, HR 0.73 (98.5% CI 0.57-0.93), P=0.002; ORR 25% vs 5%; median PFS 4.6 vs 4.4 months, HR 0.88 (0.75-1.03). At median follow-up 72 months: OS HR 0.73 (0.62-0.85), 5-year OS 26% vs 18%. FDA approval 23 November 2015.

  84. 2015 · Treatment · Kidney cancer (renal cell carcinoma)

    Cabozantinib: METEOR (after VEGF therapy) and CABOSUN (first line)

    Cabozantinib, a pill that blocks several growth signals including MET and AXL, was tested twice. After earlier VEGF-targeted therapy it delayed progression compared with everolimus (median 7.4 months against 3.8), and later survival data also favoured it. In a smaller randomised phase 2 trial of first-line treatment it was compared with sunitinib.

    METEOR (open-label phase 3, N=658, progression after VEGFR-targeted therapy): cabozantinib vs everolimus, median PFS 7.4 vs 3.8 months (first 375 patients), HR 0.58 (95% CI 0.45-0.75; P<0.001); final OS 21.4 vs 16.5 months, HR 0.66 (95% CI 0.53-0.83; P=0.00026). CABOSUN (randomised phase 2, N=157, IMDC intermediate/poor risk, first line): cabozantinib vs sunitinib, median PFS 8.2 vs 5.6 months, adjusted HR 0.66 (95% CI 0.46-0.95; one-sided P=0.012).

  85. 2015 · Treatment · Lung cancer

    PD-(L)1 blockade after chemotherapy: CheckMate, KEYNOTE-010, OAK

    After platinum chemotherapy stopped working, people with advanced lung cancer were randomly given an immune checkpoint inhibitor (nivolumab, pembrolizumab or atezolizumab) or the chemotherapy drug docetaxel. In four trials overall survival was longer with the immune drug, and severe side effects were less common. The FDA approved nivolumab in March 2015, before the first of these trials was published.

    Four randomised, open-label trials versus docetaxel after platinum-based chemotherapy. CheckMate 017 (squamous, N=272): median OS 9.2 vs 6.0 months (HR 0.59). CheckMate 057 (non-squamous, N=582): 12.2 vs 9.4 months (HR 0.73). KEYNOTE-010 (PD-L1 on at least 1% of tumour cells, N=1034): 10.4 and 12.7 vs 8.5 months. OAK (850 in the primary ITT analysis; 1225 enrolled): 13.8 vs 9.6 months (HR 0.73). Populations and PD-L1 rules differ.

  86. 2015 · Treatment · Melanoma

    Adjuvant ipilimumab 10 mg/kg: EORTC 18071 and FDA approval (2015)

    In a placebo-controlled phase 3 trial after surgery for stage III melanoma, ipilimumab at a high dose (10 mg/kg) delayed recurrence, and a later report found longer overall survival too. The cost was many more serious side effects, including immune-related deaths in about one in a hundred patients.

    Phase 3, double-blind; completely resected stage III melanoma (N=951): ipilimumab 10 mg/kg (n=475) vs placebo (n=476). Primary report: median RFS 26.1 vs 17.1 months (HR 0.75; 95% CI 0.64-0.90; P=0.0013). At median 5.3 years: 5-year OS 65.4% vs 54.4% (HR 0.72; 95.1% CI 0.58-0.88); grade 3-4 adverse events 54.1% vs 26.2%; 5 patients (1.1%) died of immune-related adverse events.

  87. 2015 · Treatment · Melanoma

    Talimogene laherparepvec (T-VEC): OPTiM trial and approval (2015)

    Talimogene laherparepvec is a modified herpes virus injected into melanoma lesions. In a randomised trial it produced lasting responses in about 16 in 100 people, against about 2 in 100 with the comparison treatment. Survival was not clearly longer, and regulators approved it for local treatment of lesions in the skin and lymph nodes.

    OPTiM, randomised open-label phase 3 (436 patients, stage IIIB to IV, unresected), intralesional T-VEC vs subcutaneous GM-CSF 2:1. Durable response rate 16.3% vs 2.1% (OR 8.9; P<.001). ORR 26.4% vs 5.7%. Median OS 23.3 vs 18.9 months (HR 0.79, 95% CI 0.62 to 1.00; P=.051). FDA and EMA approvals 2015 for local or regional lesions.

  88. 2015 · Treatment · Melanoma

    Nivolumab plus ipilimumab: CheckMate 069/067 and the 10-year follow-up

    In untreated advanced melanoma, nivolumab combined with ipilimumab, and nivolumab alone, each gave better results than ipilimumab alone. After ten years of follow-up, survival remained longer with the combination and with nivolumab. Serious side effects were more frequent with the combination. The trial was not designed to compare the combination with nivolumab alone.

    CheckMate 067 (n=945, untreated, phase 3): median PFS 11.5 months nivolumab plus ipilimumab, 6.9 nivolumab, 2.9 ipilimumab (HR 0.42 and 0.57 vs ipilimumab; 99.5% CIs). Median OS 71.9, 36.9 and 19.9 months at 10 years (HR 0.53 and 0.63); 10-year OS 43%, 37% and 19%. Not designed to compare the combination with nivolumab alone. CheckMate 069 (n=142, phase 2): response 61% vs 11% in BRAF wild-type.

  89. 2015 · Treatment · Melanoma

    KEYNOTE-006: pembrolizumab versus ipilimumab (2015, 10-year follow-up)

    In advanced melanoma, pembrolizumab given every two or three weeks was compared with ipilimumab. People on pembrolizumab went longer without progression and lived longer, with fewer severe side effects. Follow-up reports at five and ten years kept showing a survival difference, although the later reports combined the two pembrolizumab schedules.

    KEYNOTE-006 (n=834, phase 3, ipilimumab-naive): pembrolizumab 10 mg/kg every 2 or 3 weeks vs ipilimumab. 2015: 6-month PFS 47.3% and 46.4% vs 26.5% (HR 0.58); 12-month OS 74.1% and 68.4% vs 58.2%. Final OS: median 16.0 months with ipilimumab, not reached with pembrolizumab (HR 0.68 for each schedule). Pooled pembrolizumab at 10 years: median OS 32.7 vs 15.9 months (HR 0.71); 10-year OS 34.0% vs 23.6%.

  90. 2015 · Treatment · Multiple myeloma

    Daratumumab: anti-CD38 antibody from single agent to CASTOR/POLLUX

    Daratumumab is an antibody against CD38, a protein on myeloma cells. Alone, it shrank myeloma in some heavily treated people, and the US approved it in 2015. In 2016, two large trials added it to standard two-drug regimens at relapse; in each, the risk of progression or death fell by about three-fifths.

    Single-agent daratumumab 16 mg/kg: ORR 36% (GEN501, phase 1-2) and 29.2% (SIRIUS, phase 2). Relapsed myeloma, randomised phase 3, interim PFS (primary): CASTOR, Dvd versus Vd (n=498), HR 0.39 (95% CI 0.28 to 0.53); POLLUX, DRd versus Rd (n=569), HR 0.37 (0.27 to 0.52); both P<0.001. The FDA accelerated approval (2015) was followed by supplements in 2016 that fulfilled its commitments.

  91. 2015 · De-escalation · Neuroblastoma and Wilms tumour

    SIOP WT 2001: doxorubicin omitted in intermediate-risk stage II-III

    An international trial of 583 children with stage II or III Wilms tumour tested leaving out doxorubicin, which can harm the heart. About 93 in 100 children given it and about 88 in 100 not given it had no relapse or other event at two years; five-year survival was roughly 96 in 100 in both groups.

    SIOP WT 2001, open-label non-inferiority phase 3: 583 children with stage II-III intermediate-risk Wilms tumour after 4 weeks of vincristine and actinomycin D, randomised to postoperative vincristine/actinomycin D with (291) or without (292) doxorubicin. 2-year EFS 92.6% (95% CI 89.6-95.7) versus 88.2% (84.5-92.1); difference 4.4% (0.4-9.3), within the 10% margin. 5-year OS 96.5% versus 95.8%. Median follow-up 60.8 months.

  92. 2015 · Treatment · Prostate cancer

    Docetaxel with ADT in hormone-sensitive disease (CHAARTED, STAMPEDE)

    In 2015 two large trials, CHAARTED and STAMPEDE, reported longer survival when docetaxel chemotherapy was started together with hormone therapy. In CHAARTED, median survival was 57.6 months with docetaxel and 44.0 months without. A smaller French trial, GETUG-AFU 15, had found no significant survival difference.

    CHAARTED (n=790; metastatic hormone-sensitive; ADT with or without docetaxel x6): median OS 57.6 versus 44.0 months, HR 0.61 (95% CI 0.47-0.80; P<0.001). STAMPEDE (n=2962 randomized across four arms; 61% M+): docetaxel plus standard of care versus standard of care HR 0.78 (0.66-0.93; P=0.006); zoledronic acid HR 0.94 (0.79-1.11). GETUG-AFU 15 (n=385): median OS 58.9 versus 54.2 months, HR 1.01 (0.75-1.36). STAMPEDE and GETUG-AFU 15 were open-label.

  93. 2015 · Treatment · Sarcoma and GIST

    Trabectedin vs dacarbazine in liposarcoma and leiomyosarcoma

    In 518 adults with advanced liposarcoma or leiomyosarcoma that had progressed after earlier treatment, trabectedin delayed progression compared with dacarbazine (median 4.2 versus 1.5 months). Overall survival did not differ at the first analysis (12.4 versus 12.9 months) or at the final analysis, published later (13.7 versus 13.1 months).

    Phase 3 (N=518, 2:1): trabectedin (n=345) vs dacarbazine (n=173) after an anthracycline and at least one further systemic regimen. Median PFS (final analysis) 4.2 vs 1.5 months (HR 0.55; P<.001). Interim OS, the primary endpoint (64% censored): 12.4 vs 12.9 months (HR 0.87; P=.37). Final OS in a later report (577 randomised): 13.7 vs 13.1 months (HR 0.93; P=.49). FDA approval 23 October 2015.

  94. 2015 · Treatment · Thyroid cancer

    SELECT: lenvatinib for radioiodine-refractory thyroid cancer

    In people whose thyroid cancer had stopped responding to radioactive iodine, the daily oral drug lenvatinib was compared with placebo. The median time before the cancer grew was about 18 months with lenvatinib and about 4 months with placebo. About two in three on lenvatinib had tumours shrink. Side effects were common. The FDA approved it in February 2015.

    SELECT (n=392), double-blind phase 3 in progressive radioiodine-refractory thyroid cancer: lenvatinib 24 mg daily (n=261) vs placebo (n=131). Median PFS 18.3 vs 3.6 months (HR 0.21; 99% CI 0.14 to 0.31; P<0.001). Response rate 64.8% vs 1.5% (P<0.001). Median OS not reached in either group. Discontinuation for adverse effects 14.2% vs 2.3%; hypertension 67.8% with lenvatinib.

  95. 2016 · Understanding · Acute myeloid leukaemia (including APL)

    Measurable residual disease in AML: prognostic value and monitoring

    After treatment, sensitive tests can find leukaemia cells that a microscope misses; this is called measurable residual disease. Studies from 2016 linked it to a higher chance of relapse and shorter survival. A 2025 randomised trial of repeated testing during treatment found no overall survival gain, though one subgroup did better.

    Ivey 2016 (AML17, NPM1-mutated, n=346): persistent NPM1 transcripts after cycle 2 in 15%; 3-year relapse 82% v 30% (HR 4.80, 95% CI 2.95-7.80). Jongen-Lavrencic 2018 (n=482): non-DTA mutations in remission, 4-year relapse 55.4% v 31.9%. Short 2020 meta-analysis (81 publications, 11,151 patients): MRD negativity OS HR 0.36. Potter 2025 (randomised, n=637): monitoring v standard care, OS HR 1.11 (0.83-1.49); NPM1 with FLT3-ITD subgroup HR 0.53 (0.31-0.91).

  96. 2016 · De-escalation · Breast cancer

    Genomic assays guide who can skip chemotherapy

    Gene-expression tests on tumour tissue helped sort women with hormone-receptor-positive breast cancer by chemotherapy benefit. Women with no nodal disease and a mid-range score, and postmenopausal women with one to three positive nodes, did similarly well on hormone therapy alone. A 70-gene trial found a small gap in its low-risk group. Premenopausal women with positive nodes gained from chemotherapy.

    MINDACT (N=6693): high clinical risk, low genomic risk without chemotherapy had 5-year distant metastasis-free survival 94.7% (95% CI 92.5-96.2), lower limit above the 92% boundary. TAILORx (recurrence score 11-25, node-negative): iDFS HR 1.08 (0.94-1.24), endocrine vs chemoendocrine; 9-year iDFS 83.3% vs 84.3%. RxPONDER (1-3 nodes, score 25 or lower): iDFS HR (chemoendocrine vs endocrine only) 1.02 in postmenopausal and 0.60 in premenopausal women.

  97. 2016 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Blinatumomab for relapsed or refractory paediatric B-ALL

    A 2016 study tested blinatumomab, an antibody that links a patient's T cells to leukemia cells, on its own in children whose B-cell leukemia had relapsed or resisted treatment. At the dose later recommended, about two in five children reached complete remission within two cycles, and about half of those also had a complete response on residual-disease testing.

    Open-label phase I/II study of single-agent blinatumomab in 93 children (49 in phase I, 44 in phase II) with relapsed or refractory BCP-ALL. Recommended dosage 5 µg/m2/d for 7 days, then 15 µg/m2/d. Among 70 patients at that dosage, complete remission within two cycles 39% (95% CI 27 to 51); 14 of 27 (52%) had a complete MRD response. Cytokine-release syndrome of grade 3 in 3 patients (4%) and grade 4 in 1 (1%).

  98. 2016 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Dexamethasone and high-dose methotrexate in high-risk B-ALL

    In a Children's Oncology Group trial of 2,914 randomised patients aged 1 to 30 with high-risk B-cell ALL, high-dose methotrexate gave better five-year event-free survival than escalating-dose methotrexate: about 80 in 100 versus 75 in 100. Dexamethasone was linked to better outcomes in children aged 1 to 9 on high-dose methotrexate, not in older patients, who had more bone damage.

    COG AALL0232: 3,154 participants aged 1-30 with high-risk B-ALL, 2,914 randomised 2 x 2 (dexamethasone 14 days versus prednisone 28 days in induction; high-dose methotrexate versus Capizzi methotrexate plus pegaspargase in interim maintenance 1). Interim analysis, enrolment stopped: 5-year EFS 82% versus 75.4% (P=.006); mature final data 79.6% versus 75.2% (P=.008). Ages 1-9: dexamethasone plus high-dose methotrexate 91.2% versus 83.2%, 80.8%, 82.1% (P=.015). Older participants: no dexamethasone benefit, more osteonecrosis.

  99. 2016 · Treatment · Colorectal cancer

    HER2-targeted therapy for HER2-positive metastatic CRC

    A small share of bowel cancers carry extra HER2, the target of breast-cancer drugs. Four separate studies without a comparison group gave HER2-directed drugs to people whose cancer had stopped responding to standard treatment; each reported tumour responses in roughly 30 to 45 of every 100 people treated. The US provisionally approved tucatinib with trastuzumab in 2023.

    Four single-arm phase 2 studies in HER2-positive or HER2-amplified metastatic colorectal cancer, each reporting its own objective response rate (not comparable across studies): HERACLES trastuzumab + lapatinib 30% (8 of 27; 95% CI 14-50); MyPathway pertuzumab + trastuzumab 32% (18 of 57; 95% CI 20-45); DESTINY-CRC01 trastuzumab deruxtecan 45.3% (cohort A, n=53; 95% CI 31.6-59.6); MOUNTAINEER tucatinib + trastuzumab 38.1% (n=84; 95% CI 27.7-49.3).

  100. 2016 · Understanding · Glioblastoma

    WHO classification becomes molecular: IDH-wildtype glioblastoma

    The WHO classification of brain tumours began, in 2016, to define tumours by molecular features as well as by appearance under the microscope. The 2021 edition names the adult tumour glioblastoma, IDH-wildtype, and places IDH-mutant tumours in a separate astrocytoma type.

    WHO 2016: its authors describe the first CNS classification to use molecular parameters with histology; defined glioblastoma, IDH-wildtype and IDH-mutant. cIMPACT-NOW update 3 (2018): histologically grade II or III IDH-wildtype diffuse astrocytic gliomas with EGFR amplification, +7/-10 or TERT promoter mutation correspond to WHO grade IV. WHO 2021: glioblastoma, IDH-wildtype, grade 4, in adults with IDH-wildtype diffuse astrocytic glioma plus one of microvascular proliferation, necrosis, TERT promoter mutation, EGFR amplification or +7/-10; IDH-mutant astrocytoma graded 2 to 4.

  101. 2016 · De-escalation · Head and neck cancer

    Reduced-dose radiotherapy tested for good-risk HPV-positive oropharynx

    Three phase 2 studies tested giving less radiation to people with HPV-related throat cancer who had a favourable outlook. Most people in the reduced-dose groups had no progression at two years, and swallowing was better with lower doses in one study. These studies could not show that less treatment is as effective.

    Phase 2 studies in HPV-associated oropharyngeal cancer. E1308 (single arm, 80 evaluable): after induction chemotherapy and primary-site complete response, 54 Gy plus cetuximab, 2-year PFS 80% (n=51). NRG-HN002 (306 randomly assigned and eligible): 2-year PFS 90.5% with 60 Gy plus cisplatin and 87.6% with 60 Gy over 5 weeks (historical benchmark 85%). E3311 (359 evaluable): 2-year PFS 94.9% (50 Gy) and 96.0% (60 Gy) after transoral surgery.

  102. 2016 · Treatment · Head and neck cancer

    CheckMate 141: nivolumab versus standard therapy after platinum

    People whose head and neck squamous cell cancer had grown within six months of platinum chemotherapy received either the immune drug nivolumab or one standard single drug. Median survival was 7.5 months with nivolumab and 5.1 months with standard treatment, and fewer people had severe (grade 3 or 4) treatment-related side effects with nivolumab.

    Randomised open-label phase 3 (2:1; N=361): recurrent SCCHN progressing within 6 months of platinum-based chemotherapy; nivolumab 3 mg per kilogram every 2 weeks vs methotrexate, docetaxel or cetuximab. Median OS 7.5 vs 5.1 months (HR 0.70; 97.73% CI 0.51-0.96; P=0.01); 1-year OS 36.0% vs 16.6%. Median PFS 2.0 vs 2.3 months (HR 0.89; P=0.32). Response 13.3% vs 5.8%. Grade 3-4 treatment-related adverse events 13.1% vs 35.1%.

  103. 2016 · Treatment · Head and neck cancer

    Pembrolizumab after platinum: accelerated approval, then KEYNOTE-040

    Pembrolizumab, another immune drug, was approved in the United States in 2016 for head and neck cancer that had progressed on platinum chemotherapy, with approval linked to how many tumours shrank. A later randomised trial found median survival of 8.4 months with pembrolizumab and 6.9 months with standard single drugs.

    KEYNOTE-012 (phase 1b, single-arm): response rate 18% (95% CI 8-32) in 45 evaluable PD-L1-positive patients and 18% (95% CI 12-26) in a 132-patient unselected expansion cohort. FDA accelerated approval 5 August 2016. KEYNOTE-040 (phase 3, N=495, vs methotrexate, docetaxel or cetuximab): median OS 8.4 vs 6.9 months (HR 0.80; 95% CI 0.65-0.98; nominal P=0.0161). FDA fulfilled the postmarketing requirement 10 June 2019.

  104. 2016 · Treatment · Head and neck cancer

    Gemcitabine-cisplatin versus fluorouracil-cisplatin in metastatic NPC

    In China, people with nasopharyngeal cancer that had returned or spread received either gemcitabine with cisplatin or fluorouracil with cisplatin. The time before the cancer grew or the person died was longer with gemcitabine: a median of 7.0 months, compared with 5.6 months.

    Multicentre, randomised, open-label phase 3 (N=362; 22 hospitals in China): recurrent or metastatic NPC; gemcitabine plus cisplatin vs fluorouracil plus cisplatin every 3 weeks for up to 6 cycles. Median PFS (independent committee) 7.0 vs 5.6 months (HR 0.55; 95% CI 0.44-0.68; P<0.0001). Grade 3 or 4 leucopenia 29% vs 9%; mucosal inflammation 0 vs 14%.

  105. 2016 · Treatment · Hepatocellular carcinoma

    RESORCE: regorafenib after sorafenib progression

    Regorafenib was compared with placebo in 573 people with liver cancer whose disease had progressed on sorafenib and who had tolerated it. Median survival was about 11 months with regorafenib and about 8 months with placebo. The FDA approved regorafenib for this use in April 2017.

    RESORCE (double-blind phase 3, 2:1, ITT N=573): regorafenib plus best supportive care (n=379) vs placebo (n=194) in patients who had tolerated sorafenib, progressed on it, and had Child-Pugh A liver function. Median OS 10.6 vs 7.8 months, HR 0.63 (95% CI 0.50-0.79; one-sided P<0.0001).

  106. 2016 · De-escalation · Hodgkin lymphoma

    RATHL: dropping bleomycin after a negative interim PET

    In a trial registering 1,214 adults with advanced Hodgkin lymphoma, a PET scan after two ABVD cycles was negative in about five in six of those scanned. They were randomly assigned to keep or drop bleomycin. Three-year progression-free survival was about 86 in 100 with bleomycin and 84 without; respiratory side effects were more severe with bleomycin.

    Randomised trial: 1214 registered; 937 of 1119 scanned patients (83.7%) were PET-negative after two ABVD cycles and randomised to continue ABVD or omit bleomycin (AVD). Median follow-up 41 months: 3-year PFS 85.7% with ABVD versus 84.4% with AVD, difference 1.6 percentage points (95% CI -3.2 to 5.3); the authors state this fell just short of the 5-point non-inferiority margin. Respiratory adverse events were more severe with ABVD.

  107. 2016 · Treatment · Kidney cancer (renal cell carcinoma)

    Adjuvant VEGF-TKIs: ASSURE, S-TRAC, PROTECT and SORCE

    Several trials tested one to three years of VEGF-blocking tablets after kidney cancer surgery. Sunitinib delayed recurrence in one trial but not in a larger one, and pazopanib and sorafenib showed no clear benefit. Many people stopped treatment early because of side effects. The US approved sunitinib for this use in 2017.

    Adjuvant VEGF-TKI vs placebo after nephrectomy. S-TRAC (n=615, clear cell, central-review DFS): median 6.8 vs 5.6 years, HR 0.76 (95% CI 0.59-0.98; P=0.03). ASSURE (n=1943): sunitinib HR 1.02, sorafenib HR 0.97 (97.5% CI); no DFS benefit. PROTECT (pazopanib 600 mg): HR 0.86 (95% CI 0.70-1.06); final OS HR 1.0. SORCE (sorafenib 3 years): HR 1.01 (95% CI 0.83-1.23).

  108. 2016 · Treatment · Lung cancer

    KEYNOTE-024: first-line pembrolizumab for PD-L1 >= 50%

    In people with advanced lung cancer whose tumours had high levels of the PD-L1 protein and no EGFR or ALK changes, pembrolizumab alone was compared with platinum chemotherapy as first treatment. Cancer took longer to grow and survival was longer with pembrolizumab, which also caused fewer serious side effects. A later analysis kept the survival difference despite crossover.

    Open-label phase 3; previously untreated advanced NSCLC, PD-L1 on at least 50% of tumour cells, no EGFR/ALK alteration (N=305; 154 vs 151): pembrolizumab 200 mg every 3 weeks vs platinum-based chemotherapy. Median PFS 10.3 vs 6.0 months (HR 0.50; 95% CI 0.37-0.68). Updated median OS 30.0 vs 14.2 months (HR 0.63; 95% CI 0.47-0.86); 82 patients crossed over.

  109. 2016 · Treatment · Lung cancer

    Pembrolizumab plus chemotherapy first-line: KEYNOTE-021G, -189, -407

    Adding pembrolizumab to platinum chemotherapy was tested as first treatment for advanced lung cancer without EGFR or ALK changes, in non-squamous disease (KEYNOTE-189) and squamous disease (KEYNOTE-407). In both trials people lived longer and the cancer took longer to grow than with chemotherapy plus placebo. Each trial answers its own question and they are not compared.

    Two double-blind phase 3 trials of platinum chemotherapy plus pembrolizumab or placebo. Non-squamous, no EGFR/ALK alteration (KEYNOTE-189; N=616, 2:1): 12-month OS 69.2% vs 49.4% (HR 0.49; 95% CI 0.38-0.64); updated median OS 22.0 vs 10.7 months (HR 0.56). Squamous (KEYNOTE-407; N=559, 1:1): median OS 15.9 vs 11.3 months (HR 0.64; 95% CI 0.49-0.85).

  110. 2016 · De-escalation · Melanoma

    Completion node dissection vs observation: DeCOG-SLT and MSLT-II

    When a sentinel-node biopsy finds melanoma in a lymph node, surgeons had routinely removed the remaining nodes in that area. Two randomised trials compared that operation with close observation, by ultrasound in the larger trial. Survival did not differ, and in the larger trial lymphedema (swelling) was much more common after surgery.

    MSLT-II (1939 randomised; 1934 evaluable ITT; 1755 per-protocol): completion dissection vs ultrasound observation after sentinel-node metastasis; per-protocol 3-year melanoma-specific survival 86% vs 86% (P=0.42, median follow-up 43 months); disease-free survival 68% vs 63%; regional nodal control 92% vs 77%; lymphedema 24.1% vs 6.3%. DeCOG-SLT (483 randomised, closed early, underpowered): 3-year distant metastasis-free survival 74.9% (dissection) vs 77.0% (observation).

  111. 2016 · Understanding · Multiple myeloma

    Minimal residual disease: IMWG criteria to an ODAC endpoint vote

    In 2016 myeloma experts defined response categories deeper than complete response, based on searching the bone marrow for remaining cancer cells. A 2017 pooled analysis linked a negative result with longer survival. In April 2024 an advisory committee to the US drug regulator voted unanimously that this test can serve as an endpoint for accelerated approval.

    IMWG consensus (Kumar 2016) defined MRD-negative response categories, with or without imaging-based absence of extramedullary disease. A meta-analysis (Munshi 2017) found MRD negativity associated with longer PFS (14 studies, n = 1273; HR 0.41, 95% CI 0.36-0.48) and OS (12 studies, n = 1100; HR 0.57, 0.46-0.71). On 12 April 2024 FDA's ODAC voted 12 to 0 that evidence supports MRD as an accelerated approval endpoint; a draft FDA guidance followed in January 2026.

  112. 2016 · De-escalation · Neuroblastoma and Wilms tumour

    COG AREN0532 and AREN0533: risk-adapted Wilms therapy

    From 2006 the Children's Oncology Group tested treatment matched to risk. Some children with very low-risk tumours had surgery alone, and some with lung spread skipped lung radiation if scans cleared. Children with a tumour change called combined 1p and 16q loss were given stronger treatment and had better event-free survival than an earlier comparison group.

    Non-randomised COG studies. AREN0532, very low-risk (stage I FH, under 550 g, under 2 years), nephrectomy only: 116 eligible, 4-year EFS 89.7% (95% CI 84.1-95.2), OS 100%. AREN0533, lung metastases: complete response, no lung radiotherapy, EFS 79.5%, OS 96.1% (133); incomplete response, regimen M, EFS 88.5%, OS 95.4% (159). Combined LOH 1p/16q, augmented therapy: 4-year EFS 87.3% (stage I-II) and 90.2% (III-IV) versus NWTS-5 68.8% and 61.3%.

  113. 2016 · Reversal · Ovarian cancer

    Weekly paclitaxel: JGOG 3016 gain not seen in GOG-262 or ICON8

    A Japanese trial (JGOG 3016) found longer survival with weekly paclitaxel plus carboplatin than with the standard three-weekly schedule. Two later trials, GOG-262 in the United States and ICON8 in a mainly European population, did not show a significant gain in progression-free survival for weekly schedules.

    JGOG 3016 (631 analysed): dose-dense vs conventional, median PFS 28.0 vs 17.2 months (HR 0.71; 95% CI 0.58-0.88); long-term median OS 100.5 vs 62.2 months (HR 0.79; 0.63-0.99). GOG-262 (N=692): ITT median PFS 14.7 vs 14.0 months (HR 0.89; 0.74-1.06). ICON8 (N=1566): median PFS 17.7 (3-weekly), 20.8 and 21.0 months (two weekly regimens); p=0.35 and 0.51 vs 3-weekly.

  114. 2016 · Treatment · Ovarian cancer

    Niraparib and rucaparib maintenance, relapsed disease: NOVA, ARIEL3

    Two placebo-controlled trials gave a PARP inhibitor as maintenance after platinum chemotherapy for returned ovarian cancer. Niraparib (NOVA) and rucaparib (ARIEL3) both delayed progression, including in groups without a germline BRCA mutation, although the gain was smaller there. In 2022 the US recurrent-maintenance labels for both were narrowed to BRCA-mutated disease.

    NOVA (N=553): median PFS 21.0 vs 5.5 months in the germline BRCA cohort (HR 0.27), 9.3 vs 3.9 months in the non-gBRCA cohort (HR 0.45, 95% CI 0.34-0.61). ARIEL3 (N=564, investigator-assessed): BRCA-mutant 16.6 vs 5.4 months (HR 0.23); ITT 10.8 vs 5.4 months (HR 0.36, 0.30-0.45). Overall survival results are not recorded here.

  115. 2016 · Understanding · Prostate cancer

    Germline DNA-repair gene variants in metastatic prostate cancer

    Testing blood DNA from 692 men with metastatic prostate cancer found harmful inherited changes in DNA-repair genes in about 12 in 100 men (11.8%), compared with about 5 in 100 men with localised cancer (4.6%). BRCA2 was the most frequent gene. Family history and age at diagnosis did not distinguish carriers.

    Multicentre sequencing of germline DNA from 692 men with metastatic prostate cancer, unselected for family history or age, in 20 DNA-repair genes: 84 presumed-deleterious mutations in 82 men (11.8%), including BRCA2 5.3% (37 men), ATM 1.6%, CHEK2 1.9% (of 534 men with data) and BRCA1 0.9%. Localised disease: 4.6% (499 men); ExAC: 2.7% (53,105 people); both P<0.001. No difference by family history or age.

  116. 2016 · Treatment · Prostate cancer

    ProtecT: monitoring, surgery or radiotherapy for PSA-detected cancer

    A UK trial assigned about sixteen hundred men whose prostate cancer was found by PSA testing to monitoring, surgery or radiotherapy. After fifteen years, around three in a hundred men or fewer in each group had died of prostate cancer. Roughly half as many men developed metastases after surgery or radiotherapy as after monitoring, with different side-effects.

    ProtecT (n=1643, aged 50-69, PSA-detected localized disease) randomised men to active monitoring (545), prostatectomy (553) or radiotherapy (545). At median 15 years, prostate-cancer death occurred in 3.1%, 2.2% and 2.9% (P=0.53); metastases in 9.4%, 4.7% and 5.0%; clinical progression in 25.9%, 10.5% and 11.0%. Patient-reported erections sufficient for intercourse at 7 years: 18% (surgery), 30% (monitoring), 27% (radiotherapy).

  117. 2016 · De-escalation · Prostate cancer

    Shorter radiotherapy: hypofractionation and SBRT (CHHiP, PACE-B)

    Several randomised trials tested giving prostate radiotherapy in fewer, larger doses. In the largest, twenty treatments over four weeks was shown not to be worse for cancer control than thirty-seven over seven weeks, with similar long-term side-effects. Later trials tested seven or five treatments; for five-treatment stereotactic radiotherapy only two-year side-effect results are included here.

    CHHiP (n=3216): 5-year BCF-free survival 88.3% (74 Gy/37 fractions), 90.6% (60 Gy/20) and 85.9% (57 Gy/19); 60 Gy non-inferior (HR 0.84, 90% CI 0.68-1.03), 57 Gy not shown non-inferior (HR 1.20). PROFIT (60 Gy/20 vs 78 Gy/39): 85% in both arms. HYPO-RT-PC: 84% in both arms. PACE-B at 24 months, grade 2+ genitourinary toxicity 2% (conventional) vs 3% (SBRT); gastrointestinal 3% vs 2%.

  118. 2016 · Reversal · Sarcoma and GIST

    EURAMOS-1: response-adapted escalation did not improve EFS

    EURAMOS-1 tested changing osteosarcoma treatment after surgery according to how well the tumour had responded to earlier chemotherapy. For poor responders, adding two more drugs did not improve event-free survival and caused more side effects. For good responders, adding maintenance interferon was not statistically different from chemotherapy alone.

    EURAMOS-1 (2260 registered, 1334 randomised). Poor responders (618): MAP vs MAPIE, EFS HR 0.98 (95% CI 0.78-1.23), non-proportional hazards; grade 4 non-haematological toxicity 24% vs 12% with MAPIE. Good responders (716): MAP vs MAP plus pegylated interferon alfa-2b, EFS HR 0.83 (0.61-1.12; P=.214). JCOG0905 (51 vs 52 poor responders): DFS HR 1.05 (0.55-1.98), OS HR 1.48 (0.68-3.22).

  119. 2016 · Treatment · Sarcoma and GIST

    Eribulin vs dacarbazine in liposarcoma and leiomyosarcoma

    In 452 adults with advanced liposarcoma or leiomyosarcoma who had already had at least two treatments, eribulin gave longer overall survival than dacarbazine (median 13.5 versus 11.5 months). Side effects of grade 3 or higher were more common with eribulin (67% versus 56%). The US approval covers liposarcoma only.

    Open-label phase 3 (N=452; intermediate/high-grade liposarcoma or leiomyosarcoma; at least two prior regimens including an anthracycline), 1:1: eribulin 1.4 mg/m2 on days 1 and 8 (n=228) vs dacarbazine (n=224) every 21 days. Median OS (primary, ITT) 13.5 vs 11.5 months (HR 0.77; 95% CI 0.62-0.95; p=0.0169). Grade 3 or higher adverse events 67% vs 56%. FDA approval 28 January 2016 for liposarcoma only.

  120. 2016 · De-escalation · Thyroid cancer

    NIFTP: noninvasive encapsulated follicular variant renamed

    In 2016 an international group of pathologists reviewed thyroid tumours called the encapsulated follicular variant of papillary cancer. All 109 people whose tumours did not invade were alive with no evidence of disease at final follow-up, so the group proposed a new name that drops the word carcinoma and aims to reduce overtreatment.

    Nikiforov 2016 (JAMA Oncol), retrospective, 24 pathologists, slides from 13 sites in 5 countries. Noninvasive EFVPTC (n=109; median follow-up 13 years, range 10-26; 67 lobectomy only; none received radioactive iodine ablation): all alive with no evidence of disease. Invasive EFVPTC (n=101): adverse event in 12 (12%), including 5 with distant metastases, 2 died of disease. NIFTP scoring: sensitivity 98.6% (95% CI 96.3-99.4), specificity 90.1% (86.0-93.1).

  121. 2017 · Treatment · Acute myeloid leukaemia (including APL)

    CPX-351 versus 7+3 in older adults with high-risk or secondary AML

    CPX-351 packs two chemotherapy drugs, daunorubicin and cytarabine, into a fat-based particle at a fixed ratio. In a trial of 309 people aged 60 to 75 with high-risk or secondary AML, median survival was about ten months with CPX-351 and about six months with standard chemotherapy. The US approved it in August 2017.

    Lancet JE 2018 (J Clin Oncol), open-label phase 3, 309 patients aged 60-75, newly diagnosed high-risk or secondary AML: median OS 9.56 v 5.95 months, CPX-351 v 7+3 (HR 0.69, 95% CI 0.52-0.90; one-sided P=.003); overall remission rate 47.7% v 33.3% (P=.016). Five-year follow-up (Lancet Haematol 2021): median OS 9.33 v 5.95 months (HR 0.70, 0.55-0.91); 5-year OS 18% v 8%. FDA approval 3 Aug 2017.

  122. 2017 · Treatment · Acute myeloid leukaemia (including APL)

    RATIFY: midostaurin added to chemotherapy in FLT3-mutated AML

    In 2017 the US approved midostaurin, a multitargeted kinase inhibitor, to add to standard chemotherapy for adults with newly diagnosed AML with a FLT3 mutation. In the RATIFY trial of people aged 18 to 59, adding it was associated with about a 22% lower risk of death than adding a placebo.

    RATIFY: randomized, placebo-controlled phase 3 in FLT3-mutated AML aged 18-59 (n=717; 360 midostaurin, 357 placebo); daunorubicin-cytarabine induction, high-dose cytarabine consolidation, then midostaurin or placebo maintenance; transplantation allowed. OS HR 0.78 (95% CI 0.63-0.96; one-sided P=0.009); EFS HR 0.78 (0.66-0.93; one-sided P=0.002). Censoring at transplantation: OS difference not significant (P=0.08).

  123. 2017 · Treatment · Acute myeloid leukaemia (including APL)

    IDH1 and IDH2 inhibitors in AML: enasidenib, ivosidenib, olutasidenib

    From 2017 the US approved oral drugs aimed at IDH1 or IDH2 mutations in AML, beginning with enasidenib. In the AGILE trial, adults with an IDH1 mutation who could not have intensive chemotherapy had a median survival of about 24 months with ivosidenib plus azacitidine, against about 8 months with placebo plus azacitidine.

    Single-arm studies of enasidenib (IDH2; ORR 40.3%, median OS 9.3 months) and ivosidenib (IDH1; CR+CRh 30.4%, 95% CI 22.5-39.3, n=125) in relapsed or refractory AML preceded FDA approvals of each. AGILE: randomized phase 3, IDH1-mutated newly diagnosed AML ineligible for intensive chemotherapy (n=146): EFS HR 0.33 (95% CI 0.16-0.69; P=0.002); median OS 24.0 vs 7.9 months (HR 0.44, 95% CI 0.27-0.73; P=0.001).

  124. 2017 · Treatment · Bladder cancer

    KEYNOTE-045: pembrolizumab after platinum in advanced UC

    In 542 people whose advanced bladder cancer had progressed after platinum chemotherapy, pembrolizumab was linked to median survival of about 10 months compared with about 7 months for chemotherapy. Serious treatment-related side effects were less frequent with pembrolizumab.

    Open-label phase 3 (N=542; pembrolizumab n=270, chemotherapy n=272): median OS 10.3 vs 7.4 months (HR 0.73; 95% CI 0.59-0.91; P=0.002); PD-L1 CPS of 10% or more, 8.0 vs 5.2 months (HR 0.57). PFS HR 0.98 (95% CI 0.81-1.19). Grade 3-5 treatment-related events 15.0% vs 49.4%. Update: 2-year OS 26.9% vs 14.3%.

  125. 2017 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    FDA approves tisagenlecleucel for relapsed or refractory B-ALL

    In August 2017 the US regulator approved tisagenlecleucel, made from a patient's own T cells, for people up to 25 whose B-cell leukemia was refractory or in second or later relapse. About four in five patients in the main study had remission. Cytokine release syndrome occurred in about three in four, and fewer than half were event-free at three years.

    FDA regular approval (30 August 2017) for B-cell precursor ALL up to age 25, refractory or in second or later relapse. ELIANA, single-arm phase 2 (75 infused patients evaluable): overall remission rate within 3 months 81%, all responders MRD-negative; EFS 73% at 6 and 50% at 12 months; OS 90% and 76%. Three-year update (79 patients, median follow-up 38.8 months): remission rate 82%, EFS 44% (95% CI 31 to 57), OS 63% (95% CI 51 to 73).

  126. 2017 · De-escalation · Chronic myeloid leukemia

    Stopping TKIs: EURO-SKI, ENESTfreedom, ENESTop, DASFREE, label

    Four studies of stopping a TKI after a long, deep response each reported their own results. In EURO-SKI, half the 755 people evaluated had not lost major molecular response two years after stopping. Eligibility and relapse definitions differed, so percentages cannot be compared. In 2017 the US nilotinib label allowed eligible patients to be considered for stopping.

    Single-arm studies with different eligibility and relapse definitions; rates are not comparable. EURO-SKI (758 enrolled): molecular relapse-free survival (loss of MMR) 61% at 6 months, 50% at 24 months. ENESTfreedom (190 in TFR phase): 51.6% in MMR or better at 48 weeks. ENESTop: 57.9% at 48 weeks, 42.9% at 5 years. DASFREE (84 patients): 46% at 2 years, 44% at 5 years. FDA nilotinib label supplement 22 December 2017.

  127. 2017 · De-escalation · Chronic myeloid leukemia

    DESTINY: reducing the TKI dose before stopping

    In 2017 a UK trial asked whether people doing well on a TKI could safely take half the usual dose. Over 12 months about one in fourteen had a molecular recurrence, and all regained their response within four months of returning to the full dose. Recurrence was much less common in people whose response was deeper at entry.

    DESTINY (NCT01804985): non-randomised phase 2, 20 UK hospitals, 174 patients on half-dose TKI for 12 months. Interim analysis: molecular recurrence (loss of MMR on two consecutive samples) in 12 patients (7%), all regaining MMR within 4 months of full-dose resumption (median 77 days). Recurrence 2% (3/121 evaluable) in the MR4 cohort vs 19% (9/48) in the MMR cohort; hazard ratio 0.12 (90% CI 0.04-0.37; p=0.0007).

  128. 2017 · Treatment · Foundations

    First tissue-agnostic approval: pembrolizumab for MSI-H/dMMR tumours

    On 23 May 2017 the US regulator approved pembrolizumab for advanced solid tumours whose cells have a repair defect called MSI-H or dMMR, whatever organ the cancer began in. The regulator describes it as its first approval based on a tumour feature rather than a tumour site. It rested on 149 patients in five single-arm studies with no comparison group.

    FDA accelerated approval for adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumours that progressed after prior treatment with no satisfactory alternative, and for MSI-H or dMMR colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan. Basis: 149 patients in five uncontrolled single-arm trials (90 colorectal, 59 other): ORR 39.6% (95% CI 31.7 to 47.9), CR 7.4%, PR 32.2%; 78% of responses lasted 6 months or longer.

  129. 2017 · Treatment · Foundations

    First CAR T-cell therapy approved in the US: tisagenlecleucel for ALL

    On 30 August 2017 the US regulator approved tisagenlecleucel, made from a patient's own T cells, for people up to age 25 with B-cell acute lymphoblastic leukemia that had resisted treatment or relapsed twice or more. Most patients in the pivotal single-arm study had a remission, but serious immune side effects were common.

    Single-arm phase 2 (ELIANA). FDA efficacy set, 63 patients: overall remission rate within 3 months 82.5% (95% CI 70.9 to 91.0), CR 63.5%, CRi 19.0%, all MRD-negative; median follow-up 4.8 months; median duration of response not reached. Published analysis (NEJM 2018, 75 patients): remission rate 81%; EFS 73% at 6 and 50% at 12 months; cytokine release syndrome 77%, neurologic events 40%. FDA review: CRS 79%, neurologic toxicity 65%.

  130. 2017 · Treatment · Glioblastoma

    Short-course radiotherapy plus temozolomide in older people

    In 2017 a randomised trial of 562 people aged 65 or older with glioblastoma compared a short course of radiotherapy alone with the same radiotherapy plus temozolomide. Median survival was 9.3 months with temozolomide and 7.6 months without. The gain looked larger in tumours with methylated MGMT than unmethylated ones, but that difference was not statistically significant.

    CE.6 (562 randomised, age 65 or older): 40 Gy in 15 fractions with or without temozolomide. Median OS 9.3 vs 7.6 months (HR 0.67; 95% CI 0.56-0.80; P<0.001); median PFS 5.3 vs 3.9 months (HR 0.50; 0.41-0.60). MGMT methylated (n=165): OS 13.5 vs 7.7 months (HR 0.53); unmethylated (n=189): 10.0 vs 7.9 months (HR 0.75; 0.56-1.01; P=0.055; P=0.08 for interaction).

  131. 2017 · Reversal · Glioblastoma

    Adding bevacizumab to lomustine does not extend survival (EORTC 26101)

    In 2017 a trial of 437 people whose glioblastoma had progressed after first treatment added bevacizumab to lomustine chemotherapy. The cancer stayed controlled for longer on scans, but median survival was about nine months with the combination and about nine without it.

    EORTC 26101 (n=437 randomised 2:1; 288 lomustine plus bevacizumab, 149 lomustine alone) at first progression after chemoradiation: median OS 9.1 vs 8.6 months, HR 0.95 (95% CI 0.74 to 1.21; P=0.65). Locally assessed PFS 4.2 vs 1.5 months, HR 0.49 (95% CI 0.39 to 0.61). Grade 3 to 5 adverse events 63.6% vs 38.1%. MGMT status was prognostic.

  132. 2017 · Understanding · Head and neck cancer

    AJCC 8th edition stages HPV-associated oropharyngeal cancer separately

    In its eighth edition, published as a 2017 summary by the task force, the American Joint Committee on Cancer introduced a separate staging scheme for oropharyngeal cancer associated with high-risk HPV, apart from oropharyngeal cancer with other causes. The edition also reorganised chapters on the pharynx and skin.

    Lydiatt 2017 summarises the AJCC eighth edition head and neck section. Most significant change: a separate staging algorithm for high-risk HPV-associated oropharyngeal cancer. Other changes: pharynx divided into 3 chapters; cutaneous malignancies moved to a head and neck chapter; revised T categories for oral cavity, skin and nasopharynx; extranodal extension added to N category except in viral-related cancers and mucosal melanoma.

  133. 2017 · Detection · Head and neck cancer

    Plasma EBV DNA tested as a screening test for nasopharyngeal cancer

    In a 2017 Hong Kong study, more than 20,000 people with no symptoms had a blood test for Epstein-Barr virus (EBV) DNA, with repeat testing, endoscopy and MRI if it stayed positive. Thirty-four were found to have nasopharyngeal cancer, more often at an early stage than in a historical comparison group. There was no randomised control group.

    Prospective study of plasma EBV DNA screening in 20,174 participants without symptoms (registry: ethnic Chinese men aged 40 to 62). Persistently positive in 309; 34 nasopharyngeal carcinomas. Stage I or II in 71% vs 20% of a historical cohort (P<0.001); 3-year PFS 97% vs 70% (HR 0.10; 95% CI 0.05 to 0.18). Sensitivity 97.1%, specificity 98.6%. No mortality endpoint in the abstract.

  134. 2017 · Reversal · Hepatocellular carcinoma

    SARAH and SIRveNIB: no survival gain over sorafenib

    Two randomised trials compared radioembolisation (tiny radioactive beads placed in the liver's blood supply) with sorafenib tablets in people with locally advanced liver cancer. Median survival was roughly 8 to 9 months with radioembolisation and about 10 months with sorafenib, and the differences were not statistically significant.

    SARAH (France; N=467 randomised; open-label): median OS 8.0 months with SIRT vs 9.9 with sorafenib, HR 1.15 (95% CI 0.94-1.41; p=0.18). SIRveNIB (Asia-Pacific; N=360; open-label): median OS 8.8 vs 10.0 months, HR 1.1 (95% CI 0.9-1.4; P=0.36). Of those assigned to SIRT, 22% (SARAH) and 28.6% (SIRveNIB) did not receive it.

  135. 2017 · Treatment · Hepatocellular carcinoma

    Nivolumab after sorafenib: CheckMate 040 and accelerated approval

    In an early-phase trial of nivolumab in advanced liver cancer, about one in five people in the dose-expansion phase (20%) had a tumour response. In September 2017 the FDA gave accelerated approval for people previously treated with sorafenib, on condition that a randomised trial showed better survival.

    CheckMate 040 (open-label, non-comparative phase 1/2; 262 treated patients: 48 dose escalation, 214 dose expansion): objective response rate 20% (95% CI 15-26) in dose expansion (nivolumab 3 mg/kg every 2 weeks) and 15% (95% CI 6-28) in dose escalation. FDA accelerated approval 22 September 2017; postmarketing requirement 3270-1 calls for a randomised overall survival trial. FDA label: response rate 14.3% (95% CI 9.2-20.8) in a 154-patient sorafenib-treated subgroup.

  136. 2017 · De-escalation · Hodgkin lymphoma

    HD18: PET-2-guided cycles of escalated BEACOPP

    In a German trial of people with advanced Hodgkin lymphoma, a PET scan after two cycles of intensive chemotherapy (eBEACOPP) guided further treatment. Among people with a negative scan, four cycles in total gave similar five-year results to six or eight, about 92 and 91 in 100 free of progression, with fewer severe infections and organ problems.

    GHSG HD18, open-label phase 3 (2101 recruited), PET-2-guided eBEACOPP. PET-2-negative cohort (non-inferiority, 6% margin, per protocol): 5-year PFS 92.2% with 4 cycles versus 90.8% with standard 8 or 6 cycles (difference 1.4%, 95% CI -2.7 to 5.4); severe infections 8% versus 15%. PET-2-positive cohort (434 randomised): 5-year PFS 89.7% with eBEACOPP versus 88.1% with rituximab added (P=0.46).

  137. 2017 · Treatment · Hodgkin lymphoma

    ECHELON-1: brentuximab vedotin plus AVD vs ABVD

    In people with newly diagnosed advanced Hodgkin lymphoma, a regimen with the antibody-drug conjugate brentuximab vedotin in place of bleomycin lowered the chance of progression, death or an incomplete response needing further treatment at two years. A later report found fewer deaths at six years. Nerve damage and low white-cell counts were more common.

    Open-label phase 3, stage III or IV classic HL (n=1334): A+AVD versus ABVD. Primary endpoint, independently reviewed modified PFS: 2-year 82.1% versus 77.2% (HR 0.77, 95% CI 0.60 to 0.98; P=0.04). Later report, median follow-up 73.0 months: 6-year OS 93.9% versus 89.4% (HR 0.59, 95% CI 0.40 to 0.88; P=0.009). Peripheral neuropathy 67% versus 43%; primary G-CSF prophylaxis was recommended with A+AVD.

  138. 2017 · Treatment · Lung cancer

    PACIFIC: durvalumab after chemoradiotherapy, stage III

    For people with stage III lung cancer that surgery could not remove and that had not grown after chemotherapy with radiation, a year of the immune drug durvalumab was compared with placebo. Cancer took longer to grow with durvalumab, and later reports showed longer survival. More people stopped durvalumab because of side effects.

    Phase 3, randomised 2:1, placebo-controlled; unresectable stage III NSCLC without progression after chemoradiotherapy (N=713): durvalumab 10 mg per kilogram every 2 weeks for up to 12 months. Median PFS 16.8 vs 5.6 months (HR 0.52; 95% CI 0.42-0.65). OS at 24 months 66.3% vs 55.6% (HR 0.68). Exploratory 5-year update: median OS 47.5 vs 29.1 months (HR 0.72).

  139. 2017 · Treatment · Lung cancer

    FLAURA: osimertinib versus gefitinib or erlotinib, first line

    In people with untreated advanced lung cancer carrying an EGFR change, the pill osimertinib kept the cancer from growing for a median of about nineteen months, against about ten months with the older pills gefitinib or erlotinib. A later analysis also found longer survival with osimertinib.

    FLAURA (N=556), untreated EGFR exon 19 deletion/L858R advanced NSCLC, double-blind: osimertinib vs gefitinib or erlotinib. Investigator-assessed median PFS 18.9 vs 10.2 months, HR 0.46 (95% CI 0.37-0.57; P<0.001). Final OS: median 38.6 vs 31.8 months, HR 0.80 (95.05% CI 0.64-1.00; P=0.046). Grade 3 or higher adverse events 34% vs 45% at the primary analysis.

  140. 2017 · Treatment · Lung cancer

    ALEX: alectinib vs crizotinib first-line

    In ALEX, people with untreated ALK-positive lung cancer were randomly given alectinib or crizotinib. Alectinib kept the cancer from progressing for a median of 34.8 months in the later analysis, against 10.9 months with crizotinib, and brain progression was much less frequent. A final analysis of survival followed in 2025.

    ALEX (N=303; alectinib 152, crizotinib 151), untreated ALK-positive advanced NSCLC. Primary analysis: 12-month event-free rate 68.4% vs 48.7%, HR 0.47 (0.34-0.65). Mature investigator-assessed PFS: median 34.8 vs 10.9 months, HR 0.43 (0.32-0.58). Final OS: median 81.1 vs 54.2 months, HR 0.78 (0.56-1.08), interval including 1.

  141. 2017 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    ZUMA-1 and other CD19 CAR T trials in large B-cell lymphoma

    In adults whose large B-cell lymphoma had not responded to earlier treatment or had returned, three studies of CD19-directed CAR T cells reported tumour responses in about half to more than four in five of those treated. None had a comparison group. The FDA approved axicabtagene ciloleucel in October 2017.

    Single-arm studies in relapsed or refractory large B-cell lymphoma. ZUMA-1 (phase 2, 111 enrolled, 101 treated): ORR 82%, CR 54%; in an updated analysis of 108 patients treated in phases 1 and 2, 18-month OS 52%; at 5 years median OS 25.8 months, 5-year OS 42.6%. JULIET (tisagenlecleucel, 93 evaluated): best ORR 52% (95% CI 41 to 62), CR 40%. TRANSCEND NHL 001 (liso-cel, 256 efficacy-evaluable): ORR 73% (66.8 to 78.0), CR 53%.

  142. 2017 · Understanding · Non-Hodgkin lymphoma (DLBCL and follicular)

    SCHOLAR-1: outcomes in refractory DLBCL (2017)

    A pooled look back at people whose diffuse large B-cell lymphoma was refractory to treatment found that about one in four responded to the next treatment and a fifth were alive at two years. It combined data from two trials and two hospital cohorts, and is not a treatment trial.

    SCHOLAR-1: retrospective patient-level pooling of two phase 3 trials (CORAL, LY.12) and two observational cohorts; 861 patients, 636 meeting refractory-disease criteria. Objective response to the next line of therapy 26% (CR 7%); median OS 6.3 months from the start of salvage therapy; 20% alive at 2 years. Outcomes were reported as consistently poor across subgroups and cohorts.

  143. 2017 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    GALLIUM: obinutuzumab vs rituximab plus chemotherapy in FL (2017)

    In 1,202 people with untreated advanced follicular lymphoma, chemotherapy with the antibody obinutuzumab lowered the chance of progression compared with chemotherapy with rituximab: about four in five versus about three in four were progression-free at three years. Serious side effects were more common with obinutuzumab. The FDA approved it for this use in November 2017.

    Randomised phase 3 (n=1202), previously untreated advanced-stage FL: obinutuzumab-based versus rituximab-based chemotherapy, then same-antibody maintenance for up to 2 years. Planned interim analysis, median follow-up 34.5 months: investigator-assessed 3-year PFS 80.0% versus 73.3% (HR 0.66, 95% CI 0.51 to 0.85; P=0.001). Grade 3-5 adverse events 74.6% versus 67.8%. FDA approval 16 November 2017.

  144. 2017 · Treatment · Melanoma

    Adjuvant nivolumab versus ipilimumab: CheckMate 238 (2017)

    After surgery for advanced melanoma, people given the immunotherapy nivolumab stayed free of recurrence more often than those given ipilimumab at a high dose, and had far fewer serious side effects. A nine-year report did not show a clear difference in overall survival between the two drugs.

    Phase 3, double-blind; resected stage IIIB-C or IV melanoma (N=906): nivolumab 3 mg/kg every 2 weeks vs ipilimumab 10 mg/kg, up to 1 year. 12-month RFS 70.5% vs 60.8% (HR 0.65; 97.56% CI 0.51-0.83; P<0.001); grade 3-4 treatment-related adverse events 14.4% vs 45.9%. At minimum 107 months: median RFS 61.1 vs 24.2 months (HR 0.76; 95% CI 0.63-0.90); 9-year OS 69% vs 65% (HR 0.88; 95.03% CI 0.69-1.11).

  145. 2017 · Treatment · Melanoma

    Adjuvant dabrafenib plus trametinib: COMBI-AD (2017)

    For people with stage III melanoma carrying a BRAF V600E or V600K mutation, a year of dabrafenib plus trametinib after surgery kept more people free of relapse than placebo. At five years about half were alive without relapse, against about a third on placebo. Overall survival was not analysed at five years.

    Phase 3, double-blind, placebo-controlled; resected stage III BRAF V600E/K melanoma (N=870): dabrafenib 150 mg twice daily plus trametinib 2 mg daily for 12 months. 3-year RFS 58% vs 39% (HR 0.47; 95% CI 0.39-0.58; P<0.001). At 5 years RFS 52% vs 36% (HR 0.51; 95% CI 0.42-0.61) and DMFS 65% vs 54% (HR 0.55; 95% CI 0.44-0.70). 3-year OS 86% vs 77% did not cross the interim boundary.

  146. 2017 · Treatment · Multiple myeloma

    Transplant with RVD or RVD alone: IFM 2009 and DETERMINATION

    Two randomised trials asked whether people with newly diagnosed myeloma needed high-dose therapy with a stem cell transplant on top of a three-drug combination. Progression-free survival was longer with transplant in both. Overall survival was not significantly different at about four to five years. Side effects such as low white-cell counts were more common with transplant.

    IFM 2009 (n=700; RVD alone versus RVD plus high-dose melphalan and transplant; lenalidomide maintenance for 1 year): median PFS 36 versus 50 months (adjusted HR 0.65; P<0.001); OS at 4 years 82% versus 81%. DETERMINATION (357 RVD alone versus 365 transplantation; lenalidomide until progression): median PFS 46.2 versus 67.5 months (HR 1.53, RVD alone versus transplantation; 95% CI 1.23 to 1.91); 5-year survival 79.2% versus 80.7% (HR for death 1.10; 95% CI 0.73 to 1.65).

  147. 2017 · Treatment · Multiple myeloma

    Daratumumab first line without transplant: ALCYONE, MAIA, CEPHEUS

    Three trials added the CD38 antibody daratumumab to regimens for people with newly diagnosed myeloma who were not having an immediate transplant. Each reported a lower risk of progression or a higher rate of undetectable residual disease than the same regimen without it. Severe infections or pneumonia were more frequent with daratumumab in two of the trials.

    Added to VMP (ALCYONE, n=706): 18-month PFS 71.6% versus 50.2%, HR 0.50 (95% CI 0.38 to 0.65). Added to Rd (MAIA, n=737): 30-month PFS 70.6% versus 55.6%, HR 0.56; at 64.5 months median PFS 61.9 versus 34.4 months and OS HR 0.66 (0.53 to 0.83). Added to VRd (CEPHEUS, n=395; primary end point MRD negativity): 60.9% versus 39.4%; PFS HR 0.57 (0.41 to 0.79). Controls and primary end points differ.

  148. 2017 · Treatment · Neuroblastoma and Wilms tumour

    Dinutuximab beta in Europe: authorisation and the IL-2 question

    In Europe, the anti-GD2 antibody dinutuximab beta was authorised in May 2017 under exceptional circumstances. A large randomized trial reported in 2018 asked whether adding subcutaneous interleukin-2 helped: at three years about six in ten children in each group were free of relapse, progression or death, with no clear difference, and side effects were greater with interleukin-2.

    EC authorisation of dinutuximab beta (Qarziba) 8 May 2017 under exceptional circumstances. HR-NBL1/SIOPEN phase 3: 406 randomized (200 vs 206) to dinutuximab beta alone or with subcutaneous IL-2, all with isotretinoin. 3-year EFS 56% (95% CI 49 to 63) vs 60% (53 to 66), P=0.76; median follow-up 4.7 years. 62% vs 87% received allocated treatment (P<0.0001) because of toxicity.

  149. 2017 · Treatment · Neuroblastoma and Wilms tumour

    Relapsed or refractory disease: randomised phase 2 chemo-immunotherapy

    Randomized phase 2 trials tested additions to chemotherapy for neuroblastoma that returned or did not respond. In the US trial, 9 of 17 children given dinutuximab with irinotecan and temozolomide responded, against 1 of 18 given temsirolimus; the design selected a regimen for further study. European trials of bevacizumab and dinutuximab beta reported signals needing confirmation.

    ANBL1221 (randomized phase 2 selection design): ORR 53% (95% CI 29.2 to 76.7; 9/17) with irinotecan-temozolomide-dinutuximab vs 6% (0.0 to 16.1; 1/18) with temsirolimus. BEACON-Neuroblastoma (3×2 factorial, n=160): ORR 26% vs 18% with vs without bevacizumab (RR 1.52, 0.83 to 2.77; P=0.17). BEACON Immuno (n=65, 1:2): ORR 30.2% vs 18.2% with vs without dinutuximab beta; median PFS 11.1 vs 3.8 months. Primary endpoint was response.

  150. 2017 · Treatment · Pancreatic cancer

    MSI-H/dMMR tumours: pancreatic cases within tissue-agnostic evidence

    In 2017 the US regulator approved pembrolizumab for advanced solid tumours with a mismatch-repair defect, whatever the organ. Pancreatic cancer was among the most common types in a later 233-patient study, in which about one in three patients had a response. No pancreatic-only figure is given here.

    Tissue-agnostic approval (FDA accelerated approval, 23 May 2017) for MSI-H/dMMR solid tumours. KEYNOTE-158 noncolorectal cohort (phase 2, n=233, 27 tumour types; endometrial, gastric, cholangiocarcinoma and pancreatic most common): ORR 34.3% (95% CI 28.3-40.8), median PFS 4.1 months (2.4-4.9), median OS 23.5 months. Pancreatic-specific results are not in the abstract.

  151. 2017 · Understanding · Pancreatic cancer

    Borderline resectable disease gets an international definition

    A 2016 international symposium in Sendai proposed one shared definition of borderline resectable pancreatic cancer. It looks at three things: how the tumour touches blood vessels, signs that cancer may have spread, and the person's general fitness. Meeting any one of the three qualifies. The aim was to replace a definition that changed every year.

    Isaji 2018 (IAP consensus, Sendai 2016): BR-PDAC requires one or more of three dimensions. Anatomical: for example superior mesenteric or celiac artery contact under 180 degrees without stenosis or deformity. Biological: suspected but unproven metastases, nodal metastases diagnosed by biopsy or PET-CT, or CA 19-9 above 500 units/ml. Conditional: ECOG 2 or more. The NCCN adopted a definition in 2006 that changed yearly.

  152. 2017 · Treatment · Pancreatic cancer

    ESPAC-4: gemcitabine plus capecitabine as adjuvant therapy

    ESPAC-4 compared gemcitabine alone with gemcitabine plus the tablet capecitabine after pancreatic cancer surgery. Median survival was 28 months with the combination and 25.5 months with gemcitabine alone, with more severe side effects reported with the combination. The authors proposed the combination as the new standard of care.

    ESPAC-4 (Neoptolemos 2017): open-label phase 3, 730 of 732 enrolled patients analysed after R0/R1 resection of PDAC (366 gemcitabine, 364 gemcitabine plus capecitabine). Primary endpoint OS, ITT: median 28.0 months (95% CI 23.5-31.5) vs 25.5 months (22.7-27.9); HR 0.82 (95% CI 0.68-0.98), p=0.032. Reported at 458 of 480 target deaths at the data monitoring committee's request.

  153. 2017 · Treatment · Prostate cancer

    Abiraterone with ADT in hormone-sensitive disease (LATITUDE, STAMPEDE)

    In 2017 two trials added abiraterone, which blocks androgen production, to hormone therapy at the start of treatment for metastatic prostate cancer. In LATITUDE, median survival at the final analysis was 53.3 months with abiraterone and 36.5 months with placebo. The FDA approved this use for high-risk disease in February 2018.

    LATITUDE (n=1199; high-risk metastatic castration-sensitive; ADT plus abiraterone and prednisone versus ADT plus placebos): interim OS HR 0.62 (95% CI 0.51-0.76), rPFS 33.0 versus 14.8 months (HR 0.47); final OS 53.3 versus 36.5 months, HR 0.66 (0.56-0.78), with crossover allowed after the interim analysis. STAMPEDE abiraterone comparison (n=1917; 52% metastatic): OS HR 0.63 (0.52-0.76); failure-free survival HR 0.29 (0.25-0.34). Hypertension and hypokalemia were more frequent with abiraterone.

  154. 2017 · Detection · Prostate cancer

    MRI before biopsy: PROMIS and PRECISION

    Two studies tested MRI before a prostate biopsy. In PROMIS, MRI detected more clinically significant cancers than a standard ultrasound-guided biopsy but ruled fewer men out correctly. In the randomised PRECISION trial, MRI first, with a targeted biopsy only if suspicious, found more significant cancers and fewer insignificant ones than standard biopsy.

    PROMIS (576 men with PSA up to 15 ng/mL, no prior biopsy; reference template mapping biopsy): sensitivity for clinically significant cancer 93% (95% CI 88-96) for MRI vs 48% (42-55) for TRUS biopsy; specificity 41% vs 96%. PRECISION (500 randomised): clinically significant cancer 38% with MRI-targeted biopsy vs 26% with standard biopsy (adjusted difference 12 percentage points, 95% CI 4-20; P=0.005); 28% avoided biopsy. STHLM3-MRI and Goteborg-2 extend this to screening.

  155. 2017 · Treatment · Thyroid cancer

    ROAR: dabrafenib plus trametinib for BRAF V600E anaplastic cancer

    Anaplastic thyroid cancer is rare and fast-growing. In a single-arm study of people whose tumours carried a BRAF V600E mutation, dabrafenib plus trametinib shrank tumours in about two in three of the first 16 people assessed, and in just over half of the full group of 36 on later analysis. The FDA approved the combination in 2018.

    ROAR anaplastic thyroid cancer cohort (open-label phase 2 basket, BRAF V600E; dabrafenib 150 mg twice daily plus trametinib 2 mg daily). First report: 16 evaluable patients, confirmed ORR 69% (11 of 16; 95% CI 41 to 89), 12-month PFS 79% and OS 80%. Updated analysis, 36 patients (cutoff 14 September 2020): ORR 56% (95% CI 38.1 to 72.1), median PFS 6.7 and OS 14.5 months, 12-month OS 51.7%.

  156. 2018 · Treatment · Acute myeloid leukaemia (including APL)

    Venetoclax with azacitidine for unfit AML (VIALE-A)

    In 2018 the US approved venetoclax, a tablet, together with azacitidine, decitabine or low-dose cytarabine for adults with newly diagnosed AML who could not have intensive chemotherapy. In the later VIALE-A trial, people given venetoclax with azacitidine lived a median of about 15 months, compared with about 10 months on azacitidine alone.

    VIALE-A: randomized, double-blind phase 3, AML ineligible for intensive induction (age 75 or older or comorbidities); ITT 431 (286 azacitidine-venetoclax, 145 azacitidine-placebo). Median OS 14.7 vs 9.6 months (HR 0.66, 95% CI 0.52-0.85; P<0.001), median follow-up 20.5 months; CR 36.7% vs 17.9%; CR+CRi 66.4% vs 28.3%. VIALE-C (venetoclax plus LDAC, n=211): planned OS analysis HR 0.75 (95% CI 0.52-1.07; P=.11).

  157. 2018 · Treatment · Acute myeloid leukaemia (including APL)

    ADMIRAL: gilteritinib versus salvage chemotherapy, FLT3-mutated AML

    In 2018 the US approved gilteritinib, a FLT3 inhibitor taken by mouth, for AML that had come back or not responded to treatment and carried a FLT3 mutation. In the ADMIRAL trial, median survival was about 9 months with gilteritinib and about 6 months with salvage chemotherapy.

    ADMIRAL: randomized (2:1) phase 3 of gilteritinib 120 mg/day vs salvage chemotherapy in relapsed or refractory FLT3-mutated AML (371 eligible; 247 vs 124). Median OS 9.3 vs 5.6 months (HR 0.64, 95% CI 0.49-0.83; P<0.001); CR/CRh 34.0% vs 15.3%; CR 21.1% vs 10.5%; median EFS 2.8 vs 0.7 months (HR 0.79, 95% CI 0.58-1.09).

  158. 2018 · Treatment · Breast cancer

    KATHERINE: T-DM1 for residual disease after neoadjuvant therapy

    For people with HER2-positive early breast cancer who still had invasive cancer at surgery after pre-operative treatment, switching to trastuzumab emtansine instead of continuing trastuzumab lowered the risk of the cancer coming back. A later report also reported a lower risk of death.

    Phase 3 (1,486 patients) with residual invasive disease after neoadjuvant taxane plus trastuzumab: adjuvant T-DM1 vs trastuzumab for 14 cycles. Interim: 3-year iDFS 88.3% vs 77.0% (HR 0.50; 95% CI 0.39 to 0.64; P<0.001). Final iDFS (median follow-up 8.4 years): HR 0.54 (95% CI 0.44 to 0.66); 7-year 80.8% vs 67.1%. Second interim OS: HR 0.66 (95% CI 0.51 to 0.87; P=0.003); 7-year 89.1% vs 84.4%.

  159. 2018 · Reversal · Cervical cancer

    LACC: lower survival with minimally invasive radical hysterectomy

    Surgeons had adopted keyhole and robot-assisted radical hysterectomy before good survival data existed. In a randomised trial of women with early-stage cervical cancer, those having keyhole surgery were more likely to have the cancer return or to die than those having open surgery, and the trial authors later concluded open surgery should be standard.

    LACC (319 minimally invasive vs 312 open radical hysterectomy; stage IA1 with LVSI, IA2, IB1): 4.5-year DFS 86.0% vs 96.5% (difference -10.6 points; 95% CI -16.4 to -4.7; non-inferiority margin -7.2), HR 3.74 (1.63 to 8.58). 3-year OS 93.8% vs 99.0%, HR 6.00 (1.77 to 20.30). Final analysis: 4.5-year OS 90.6% vs 96.2%, HR 2.71 (1.32 to 5.59).

  160. 2018 · Reversal · Cervical cancer

    Neoadjuvant chemotherapy then surgery did not replace chemoradiation

    Two randomised trials compared giving chemotherapy first and then operating with standard chemoradiation for stage IB2 to IIB cervical cancer. Neither showed that chemotherapy followed by surgery was better: one found worse disease-free survival, the other no difference in five-year survival.

    Single-centre phase III (N=635; squamous IB2-IIB): neoadjuvant paclitaxel-carboplatin then radical hysterectomy vs cisplatin chemoradiation: 5-year DFS 69.3% vs 76.7%, HR 1.38 (95% CI 1.02 to 1.87; P=.038); 5-year OS 75.4% vs 74.7%, HR 1.025 (0.752 to 1.398). EORTC 55994 (N=626): 5-year OS 72% (66 to 77) vs 76% (70 to 80), not significantly different.

  161. 2018 · Detection · Cervical cancer

    HPV self-sampling: meta-analysis, mailed kits and FDA actions

    HPV testing can be done on a sample women collect themselves. A meta-analysis found PCR-based tests about as sensitive on self samples as on clinician samples, and mailed kits reached more under-screened women than letters. In a US trial, roughly 26 in 100 women screened after a mailed kit versus 17 in 100 with usual reminders.

    Meta-analysis (Arbyn 2018; 56 accuracy studies, 25 participation trials): PCR-based hrHPV assays on self vs clinician samples, pooled sensitivity ratio 0.99 (95% CI 0.97-1.02) for CIN2+ or CIN3+; mailed kits vs invitation or reminder letters, relative participation 2.33 (1.86-2.91). HOME RCT (n=19,851): screening uptake 26.3% vs 17.4%, RR 1.51 (1.43-1.60); CIN2+ detection 12 vs 8, RR 1.49 (0.61-3.64). May 2024: FDA approved self-collected vaginal specimens obtained in a healthcare setting as an alternative specimen type.

  162. 2018 · Detection · Cervical cancer

    US screening guidance adds primary HPV testing (USPSTF 2018, ACS 2020)

    In 2018 the US Preventive Services Task Force recommended, for women aged 30 to 65, screening with cytology every three years, HPV testing alone every five years, or both together every five years. In 2020 the American Cancer Society preferred primary HPV testing every five years, starting at age 25.

    USPSTF (August 2018, grade A): women 21-29, cytology every 3 years; women 30-65, cytology every 3 years, hrHPV testing alone every 5 years, or cotesting every 5 years. ACS 2020 guideline update (average risk): start at 25; primary HPV testing every 5 years through 65 preferred; cotesting every 5 years or cytology every 3 years acceptable where primary testing is not available; stop after 65 with adequate negative prior screening.

  163. 2018 · Treatment · Cervical cancer

    KEYNOTE-158: pembrolizumab approved for PD-L1-positive disease (2018)

    In a phase 2 study of 98 people with previously treated advanced cervical cancer, the immune checkpoint drug pembrolizumab shrank tumours in about one in eight, all of them with PD-L1-positive tumours. In June 2018 the FDA granted accelerated approval; a 2021 letter later recorded the commitments as fulfilled.

    Phase 2 basket study, cervical cohort (n=98 treated): pembrolizumab 200 mg every 3 weeks. ORR 12.2% (95% CI 6.5-20.4); three complete and nine partial responses, all in PD-L1-positive tumours (CPS 1 or more, n=82): ORR 14.6% (95% CI 7.8-24.2). Median duration of response not reached; median follow-up 10.2 months. FDA accelerated approval 12 June 2018; Subpart E fulfilled 13 October 2021.

  164. 2018 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Dasatinib with chemotherapy for Ph-positive ALL

    Dasatinib is a more potent BCR-ABL1 blocker than imatinib. In a Children's Oncology Group study of 60 patients aged 1 to 30, adding it to intensive chemotherapy was feasible, with outcomes similar to the earlier imatinib study. A randomised trial in China reported better event-free survival with dasatinib than imatinib.

    COG AALL0622 (single-arm, n=60, ages 1-30): dasatinib from induction day 15 plus intensive chemotherapy; 5-year EFS 60%, OS 86%; 5-year CNS relapse incidence 15.4% in 40 non-transplanted, non-CNS3 patients; 5-year DFS 60% vs 68% for AALL0031 imatinib (P=0.31). CA180-372/AALL1122 (n=106): 3-year EFS 65.5% vs 49.2% historical chemotherapy alone (p=0.032) and 59.1% historical imatinib (p=0.27). Randomised China trial (n=189): 4-year EFS 71.0% vs 48.9% (p=0.005).

  165. 2018 · De-escalation · Colorectal cancer

    IDEA: 3 versus 6 months of adjuvant oxaliplatin chemotherapy

    Six randomised trials were pooled to ask whether three months of oxaliplatin chemotherapy after surgery for stage III colon cancer works as well as six months, with less nerve damage. Overall, the pooled analysis could not confirm that three months was as good. For the CAPOX regimen it met the standard set in advance, but for FOLFOX it did not.

    IDEA pooled analysis (Grothey 2018): six phase 3 trials, 12,834 patients with stage III colon cancer, 3 vs 6 months of FOLFOX or CAPOX. Noninferiority (upper CI limit 1.12) was not confirmed overall (HR 1.07, 95% CI 1.00-1.15); seen for CAPOX (HR 0.95, 0.85-1.06), not FOLFOX (HR 1.16, 1.06-1.26). Final 5-year OS 82.4% vs 82.8% (HR 1.02, 0.95-1.11; noninferiority p=0.058).

  166. 2018 · Treatment · Colorectal cancer

    Fruquintinib for refractory metastatic CRC (FRESCO and FRESCO-2)

    Fruquintinib is a capsule that blocks the receptors for a blood-vessel growth signal. A trial in China and a larger international trial each compared it with placebo in people whose bowel cancer had progressed after standard treatments, and each found longer survival with fruquintinib.

    FRESCO (double-blind phase 3, China, n=416, 2:1): median OS 9.3 vs 6.6 months, fruquintinib vs placebo (HR 0.65, 95% CI 0.51-0.83; P<0.001). FRESCO-2 (double-blind phase 3, 14 countries, n=691, 2:1, progressed on or intolerant to trifluridine-tipiracil or regorafenib or both): median OS 7.4 vs 4.8 months (HR 0.66, 95% CI 0.55-0.80; P<0.0001). Grade 3 or worse adverse events 63% vs 50% in FRESCO-2.

  167. 2018 · Treatment · Endometrial cancer

    PORTEC-3: chemoradiotherapy versus radiotherapy, high-risk disease

    In women with high-risk endometrial cancer, pelvic radiotherapy alone was compared with radiotherapy plus chemotherapy. At five years survival did not differ significantly, but more women were free of failure with chemotherapy, at the cost of more side effects. A ten-year report found higher survival with chemotherapy.

    Open-label phase 3 (686 enrolled; 660 eligible): chemoradiotherapy (pelvic RT 48.6 Gy with cisplatin, then carboplatin-paclitaxel) vs pelvic RT alone. Co-primary endpoints, chemoradiotherapy vs RT: 5-year OS 81.8% vs 76.7% (adjusted HR 0.76, 95% CI 0.54-1.06; p=0.11) and FFS 75.5% vs 68.6% (HR 0.71, 0.53-0.95; p=0.022). Grade 3 or worse adverse events during treatment 60% vs 12%. Preplanned 10-year analysis: OS 74.4% vs 67.3% (HR 0.73, 0.54-0.97; p=0.032).

  168. 2018 · Treatment · Endometrial cancer

    Trastuzumab with chemotherapy in HER2-positive uterine serous cancer

    In a small randomised phase 2 trial in advanced or recurrent HER2-positive uterine serous carcinoma, adding trastuzumab to carboplatin and paclitaxel was compared with chemotherapy alone. Cancer took longer to progress with trastuzumab, and an update reported longer survival. The trial was small and used one-sided statistical tests.

    Randomised phase 2, 61 patients (58 evaluable), HER2 IHC 3+ or 2+/FISH-amplified uterine serous carcinoma; carboplatin-paclitaxel with or without trastuzumab. Median PFS 8.0 vs 12.6 months (HR 0.44; 90% CI 0.26-0.76; one-sided P=0.005). Update: PFS 8.0 vs 12.9 months (HR 0.46); median OS 24.4 vs 29.6 months (HR 0.58; 90% CI 0.34-0.99; P=0.046). One-sided log-rank tests, 90% CIs.

  169. 2018 · Reversal · Head and neck cancer

    Cetuximab worse than cisplatin with radiotherapy, HPV-positive cancer

    Two trials in HPV-related throat cancer asked whether cetuximab could replace cisplatin alongside radiation to reduce side effects. In both, people given cetuximab did worse on survival or cancer control, and neither trial found a clear side-effect advantage for cetuximab. Both teams recommended cisplatin as the standard of care.

    Two phase 3 trials in HPV-positive oropharyngeal cancer compared radiotherapy with cetuximab vs cisplatin. RTOG 1016 (849 randomised; non-inferiority margin 1.45): OS HR 1.45 (one-sided 95% upper CI 1.94), 5-year OS 77.9% (cetuximab) vs 84.6% (cisplatin); PFS HR 1.72 (95% CI 1.29-2.29). De-ESCALaTE (N=334, low risk): severe toxicity events did not differ (4.8 vs 4.8 per patient); 2-year OS 89.4% (cetuximab) vs 97.5% (cisplatin).

  170. 2018 · Treatment · Hepatocellular carcinoma

    REFLECT: lenvatinib non-inferior to sorafenib first line

    Lenvatinib was compared with sorafenib in 954 people with unresectable liver cancer who had had no drug treatment for advanced disease. Median survival was about 14 months with lenvatinib and 12 months with sorafenib. The trial was built to show lenvatinib was not worse, and it met that aim. The FDA approved it in August 2018.

    REFLECT (open-label phase 3 non-inferiority, ITT N=954, no prior treatment for advanced disease): lenvatinib (n=478) vs sorafenib (n=476). Median OS 13.6 vs 12.3 months, HR 0.92 (95% CI 0.79-1.06); the non-inferiority margin of 1.08 was met. Primary endpoint OS; the abstract reports no superiority test.

  171. 2018 · Treatment · Hepatocellular carcinoma

    CELESTIAL: cabozantinib after prior systemic therapy

    Cabozantinib was compared with placebo in 707 people with advanced liver cancer who had already received sorafenib and could have had up to two earlier drug treatments. Median survival was about 10 months with cabozantinib and 8 months with placebo. Severe (grade 3 or 4) side effects were about twice as common with cabozantinib.

    CELESTIAL (double-blind phase 3, 2:1, ITT N=707: 470 vs 237): cabozantinib 60 mg daily vs placebo after prior sorafenib (up to two previous regimens for advanced disease). Second planned interim analysis: median OS 10.2 vs 8.0 months, HR 0.76 (95% CI 0.63-0.92; P=0.005); median PFS 5.2 vs 1.9 months, HR 0.44 (95% CI 0.36-0.52); ORR 4% vs under 1% (P=0.009). Grade 3 or 4 adverse events: 68% vs 36%.

  172. 2018 · Treatment · Hepatocellular carcinoma

    Pembrolizumab: KEYNOTE-224, -240 and -394 and the FDA label

    Pembrolizumab was tested in three trials after earlier treatment, mostly sorafenib. In a single-arm study, 17% of 104 people had a tumour response. One placebo-controlled trial did not reach its prespecified thresholds; another, in people from Asia, reported longer median survival (14.6 versus 13.0 months). The FDA label was later revised to hepatitis B-related disease.

    KEYNOTE-224 (single-arm phase 2, n=104): ORR 17% (95% CI 11-26). KEYNOTE-240 (double-blind phase 3, N=413): median OS 13.9 vs 10.6 months, HR 0.781 (95% CI 0.611-0.998; one-sided P=0.0238 vs threshold 0.0174); authors: OS and PFS did not reach specified significance. KEYNOTE-394 (Asia, N=453): median OS 14.6 vs 13.0 months, HR 0.79 (95% CI 0.63-0.99; P=0.0180 vs threshold 0.0193).

  173. 2018 · Treatment · Kidney cancer (renal cell carcinoma)

    CheckMate 214: nivolumab plus ipilimumab versus sunitinib (2018)

    In people with previously untreated advanced clear cell kidney cancer, nivolumab plus ipilimumab was compared with sunitinib. In the intermediate- and poor-risk group, survival and response rates were higher with the combination. Follow-up now exceeds nine years. The FDA approved the combination for that risk group in April 2018.

    CheckMate 214 (phase 3, n=1096; intermediate/poor risk 425 vs 422): OS HR 0.63 (99.8% CI 0.44-0.89), 18-month OS 75% vs 60%; ORR 42% vs 27%; median PFS 11.6 vs 8.4 months, HR 0.82, P=0.03 (not significant at the 0.009 threshold). At 9.3 years' median follow-up, OS HR 0.69 (0.59-0.81); 108-month OS 30.2% vs 18.7%. FDA approval 16 April 2018, intermediate/poor risk.

  174. 2018 · Reversal · Kidney cancer (renal cell carcinoma)

    CARMENA and SURTIME question upfront cytoreductive nephrectomy

    For about twenty years, removing the kidney was standard for people whose kidney cancer had already spread. In CARMENA, sunitinib alone was found not inferior to surgery first for survival (a median of about eighteen months against fourteen). A smaller trial, SURTIME, found no difference in early progression between operating first or after sunitinib.

    CARMENA (phase 3, 450 patients, clear cell, MSKCC intermediate/poor risk): sunitinib alone was noninferior to nephrectomy then sunitinib for OS at a planned interim analysis, stratified HR 0.89 (95% CI 0.71-1.10; non-inferiority bound 1.20 or less); median OS 18.4 vs 13.9 months. SURTIME (99 patients): 28-week progression-free rate 42% vs 43% (immediate vs deferred nephrectomy), P=0.61; OS HR 0.57 (95% CI 0.34-0.95), a secondary end point.

  175. 2018 · Treatment · Lung cancer

    Extensive-stage SCLC: chemotherapy plus atezolizumab or durvalumab

    Two randomised trials added an immune checkpoint inhibitor, atezolizumab or durvalumab, to platinum-etoposide chemotherapy for newly diagnosed extensive-stage small-cell lung cancer. Typical survival was about two to three months longer with the added drug: around 12 months versus 10 in one trial, and 13 versus 10 in the other. The trials were run separately and are not compared.

    IMpower133 (double-blind; atezolizumab 201 vs placebo 202, each with carboplatin-etoposide): median OS 12.3 vs 10.3 months (HR 0.70; 95% CI 0.54-0.91; P=0.007); median PFS 5.2 vs 4.3 months. CASPIAN (open-label; durvalumab plus platinum-etoposide vs platinum-etoposide, planned interim analysis): median OS 13.0 vs 10.3 months (HR 0.73; 0.59-0.91; P=0.0047); 18-month OS 34% vs 25%. Separate trials; not directly comparable.

  176. 2018 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    RELEVANCE: rituximab-lenalidomide vs chemoimmunotherapy (2018)

    In 1,030 people with untreated advanced follicular lymphoma, a chemotherapy-free pairing of lenalidomide with rituximab gave similar results to rituximab with chemotherapy, with different side effects: fewer low neutrophil counts but more skin reactions. At six years about six in ten people were free of progression in both groups.

    Randomised phase 3 superiority trial (n=1030), untreated FL: rituximab-lenalidomide (R2) versus rituximab-chemotherapy, both followed by rituximab maintenance. Complete response (confirmed or unconfirmed) at 120 weeks 48% versus 53% (P=0.13); interim 3-year PFS 77% versus 78%. At median follow-up 72 months: 6-year PFS 60% versus 59% (HR 1.03, 95% CI 0.84 to 1.27); 6-year OS 89% in both.

  177. 2018 · Treatment · Melanoma

    Adjuvant pembrolizumab: EORTC 1325/KEYNOTE-054 (2018)

    After surgery for high-risk stage III melanoma, a year of pembrolizumab kept more people free of recurrence than placebo, and the benefit was still seen after a median follow-up of almost seven years. Serious side effects were more common with pembrolizumab. The reports summarised here give no overall survival result.

    Phase 3, double-blind; resected stage III melanoma (N=1,019): pembrolizumab 200 mg every 3 weeks (n=514) vs placebo (n=505), up to 18 doses. 12-month RFS 75.4% vs 61.0% (HR 0.57; 98.4% CI 0.43-0.74; P<0.001). Distant metastasis-free survival at 3.5 years 65.3% vs 49.4% (HR 0.60; 95% CI 0.49-0.73). At median 6.9 years, 7-year RFS 50% vs 36% (HR 0.63; 95% CI 0.53-0.74).

  178. 2018 · Treatment · Melanoma

    Neoadjuvant checkpoint blockade: OpACIN, OpACIN-neo and PRADO

    Small early studies gave ipilimumab plus nivolumab before surgery to people with stage III melanoma. Most had a pathological response, but the first schedule caused frequent serious side effects. A lower-ipilimumab schedule had fewer, though the small comparison could not confirm this, and a later cohort used response to guide treatment.

    OpACIN (n=20, 1:1): neoadjuvant vs adjuvant ipilimumab 3 mg/kg plus nivolumab 1 mg/kg; pathological response 7/9 (78%) in the neoadjuvant arm. OpACIN-neo (phase 2, 89 randomised): grade 3-4 immune-related adverse events 40%, 20%, 50% and pathological response 80%, 77%, 65% in groups A, B (ipilimumab 1 mg/kg plus nivolumab 3 mg/kg) and C. PRADO (n=99): pathological response 72%; 24-month RFS 93% (major response).

  179. 2018 · Treatment · Melanoma

    Brain metastases: ipilimumab-nivolumab trials (ABC, CheckMate 204)

    Brain metastases had been excluded from many melanoma trials. Two phase 2 studies gave nivolumab with ipilimumab to people with untreated brain metastases and saw shrinkage or disease control in about half. In a small randomised comparison, the combination had a higher intracranial response rate than nivolumab alone, without a formal test. Side effects were frequent.

    ABC (randomised phase 2, n=79 enrolled): intracranial response 46% (nivolumab plus ipilimumab), 20% (nivolumab), 6% (non-randomised cohort C); at 7 years OS 48%, 26% and 13%. CheckMate 204 (single-arm, n=94): intracranial clinical benefit 57% (95% CI 47 to 68); grade 3 or 4 treatment-related adverse events 55%.

  180. 2018 · Detection · Oesophageal cancer

    Barrett oesophagus: AspECT, BEST3 and BOSS randomised trials

    Three randomised trials, run mainly in the UK, looked at Barrett oesophagus, a change in the lining of the gullet linked to oesophageal adenocarcinoma. One tested acid-suppressing medicine with or without aspirin, one tested a swallowable sponge test for finding Barrett oesophagus, and one found that regular surveillance endoscopy did not improve survival compared with endoscopy only when needed.

    AspECT (N=2557, 2x2 factorial, median follow-up 8.9 years): high-dose vs low-dose esomeprazole time ratio 1.27 (95% CI 1.01 to 1.58) for death, adenocarcinoma or high-grade dysplasia; aspirin 1.24 (0.98 to 1.57; P=0.068). BEST3 (13,514 randomised): Barrett oesophagus diagnosed in 140 of 6834 vs 13 of 6388 within 12 months (rate ratio 10.6). BOSS (3453): overall survival HR 0.95 (95% CI 0.82 to 1.10), surveillance vs endoscopy at need.

  181. 2018 · Treatment · Ovarian cancer

    SOLO-1: first-line olaparib maintenance for BRCA-mutated disease

    After surgery and chemotherapy for newly diagnosed advanced ovarian cancer, people whose tumours carried a BRCA mutation took olaparib or placebo as maintenance. Three years on, about three in five on olaparib had no progression, against about one in four on placebo. Seven-year follow-up suggested longer survival, which did not meet the prespecified significance threshold.

    SOLO-1 (N=391, 2:1, BRCA1/2-mutated, stage III-IV, after platinum response): freedom from progression and death at 3 years 60% vs 27%, HR 0.30 (95% CI 0.23-0.41). Post-hoc 5-year update: median PFS 56.0 vs 13.8 months, HR 0.33 (0.25-0.43). Prespecified 7-year OS: HR 0.55 (0.40-0.76), p=0.0004 (p<0.0001 required); 67.0% vs 46.5% alive.

  182. 2018 · Treatment · Ovarian cancer

    HIPEC added to interval cytoreductive surgery: OVHIPEC-1

    Hyperthermic intraperitoneal chemotherapy (HIPEC) means bathing the abdomen in heated chemotherapy during surgery. A 2018 randomised trial of 245 women added it to interval surgery and reported longer time without recurrence and longer survival. A later Korean trial found no overall benefit, and a trial in relapsed disease again reported longer survival.

    OVHIPEC-1 (245 patients, stage III, interval surgery after three cycles of carboplatin-paclitaxel): median recurrence-free survival 14.2 vs 10.7 months (HR 0.66, 95% CI 0.50 to 0.87); median OS 45.7 vs 33.9 months (HR 0.67, 0.48 to 0.94). KOV-HIPEC-01 (184): no significant overall PFS or OS difference; interval-surgery subgroup OS HR 0.53 (0.29 to 0.96). CHIPOR (415, first relapse): median OS 54.3 vs 45.8 months (HR 0.73, 0.56 to 0.96).

  183. 2018 · Treatment · Pancreatic cancer

    PRODIGE 24: adjuvant modified FOLFIRINOX versus gemcitabine

    PRODIGE 24 compared a four-drug chemotherapy, modified FOLFIRINOX, with gemcitabine after pancreatic cancer surgery. Median survival was about 54 months with the four-drug regimen and 35 months with gemcitabine. Severe side effects were more common with the four-drug regimen, in about three of four people against about half.

    PRODIGE 24 / CCTG PA6 (Conroy 2018): 493 patients with resected PDAC randomised to modified FOLFIRINOX or gemcitabine for 24 weeks. Primary endpoint DFS: median 21.6 vs 12.8 months (stratified HR 0.58, 95% CI 0.46-0.73). Median OS 54.4 vs 35.0 months (HR 0.64, 95% CI 0.48-0.86, P=0.003). Grade 3 or 4 adverse events 75.9% vs 52.9%. At 69.7 months, OS HR 0.68 (0.54-0.85).

  184. 2018 · Treatment · Prostate cancer

    AR inhibitors and metastasis-free survival in non-metastatic CRPC

    Three trials, SPARTAN, PROSPER and ARAMIS, tested androgen-receptor inhibitors in men with non-metastatic castration-resistant prostate cancer and a rapidly rising PSA. Each reported longer metastasis-free survival than placebo, for example 40.5 months with apalutamide against 16.2 months. Later reports of overall survival also favored each drug.

    Non-metastatic CRPC on conventional imaging, PSA doubling time 10 months or less, placebo-controlled (2:1) with continued ADT. Metastasis-free survival: SPARTAN (n=1207) 40.5 versus 16.2 months, HR 0.28 (95% CI 0.23-0.35); PROSPER (n=1401) 36.6 versus 14.7 months, HR 0.29 (0.24-0.35); ARAMIS (n=1509) 40.4 versus 18.4 months, HR 0.41 (0.34-0.50). Final overall survival HRs: SPARTAN 0.78 (0.64-0.96), PROSPER 0.73 (0.61-0.89), ARAMIS 0.69 (0.53-0.88).

  185. 2018 · Understanding · Testicular germ cell tumors

    Cumulative burden of morbidity after cisplatin-based chemotherapy

    A 2018 multi-centre study of more than 1,200 men who had finished standard cisplatin-based chemotherapy for testicular cancer scored their combined load of long-term health problems. About one in five had a high or very high score, and some problems, such as hearing loss and tinnitus, tended to occur together.

    Kerns 2018: 1,214 men aged 55 or younger at diagnosis, at least 1 year after first-line chemotherapy. Cumulative burden of morbidity score: low or very low 47%, medium 30%, high 15%, very high or severe 4.1% (as published; sum 96.1%). Higher scores were associated with four cycles of BEP (OR 1.44, 95% CI 1.04 to 1.98) or IEP (OR 1.96, 1.04 to 3.71), reference group not stated in the abstract; score did not differ between regimens (P = .36).

  186. 2018 · Treatment · Thyroid cancer

    NTRK fusions: larotrectinib and entrectinib across tumour types

    Fusions of the NTRK genes occur in many kinds of cancer, including some thyroid cancers. In single-arm studies the TRK inhibitors larotrectinib and entrectinib shrank tumours in about three-quarters and just over half of people across many tumour types. Among 28 people with TRK fusion-positive thyroid cancer who could be evaluated, larotrectinib shrank tumours in about seven in ten.

    Larotrectinib, three protocols pooled: ORR 75% (95% CI 61-85) by independent review in the first 55 patients; 79% (72-85) by investigator in 153 evaluable of 159 treated. Entrectinib, integrated analysis (54 adults): ORR 57% (43.2-70.8), median DOR 10 months. TRK fusion-positive thyroid carcinoma (larotrectinib, 29 treated, 28 evaluable): ORR 71% (51-87); 86% (64-97) in papillary or follicular, 29% (4-71) in anaplastic.

  187. 2019 · Treatment · Bladder cancer

    Enfortumab vedotin after platinum and PD-1/PD-L1: EV-201, EV-301

    Enfortumab vedotin is an antibody-drug conjugate aimed at a protein called Nectin-4. In a phase 2 study, tumours shrank in about four in ten people whose bladder cancer had progressed after platinum and immunotherapy. In a randomised trial of 608 people, median survival was about 13 months versus about 9 with chemotherapy.

    EV-201 (phase 2, single-arm, cohort 1, n=125): confirmed ORR 44% (95% CI 35.1-53.2), 12% complete responses; median DOR 7.6 months. EV-301 (phase 3, N=608): median OS 12.88 vs 8.97 months (HR 0.70; 95% CI 0.56-0.89; P=0.001); median PFS 5.55 vs 3.71 months (HR 0.62). EV-201 cohort 2 (n=89, cisplatin-ineligible): ORR 52%.

  188. 2019 · Treatment · Bladder cancer

    Erdafitinib for FGFR-altered urothelial cancer: BLC2001 to THOR

    Erdafitinib is a tablet that blocks FGFR proteins. In a phase 2 study, 40 in every 100 people with FGFR-altered advanced bladder cancer had a response. In a later randomised trial after immunotherapy, median survival was about 12 months with erdafitinib versus about 8 with chemotherapy.

    BLC2001 (phase 2, n=99 selected regimen): confirmed ORR 40%; median PFS 5.5 and OS 13.8 months. THOR cohort 1 (phase 3, N=266, after anti-PD-1/PD-L1): median OS 12.1 vs 7.8 months (HR 0.64; 95% CI 0.47-0.88; P=0.005); PFS 5.6 vs 2.7 months. THOR cohort 2 (N=351, vs pembrolizumab): OS 10.9 vs 11.1 months (HR 1.18; 95% CI 0.92-1.51).

  189. 2019 · Treatment · Breast cancer

    PI3K/AKT pathway inhibitors after endocrine therapy

    After hormone therapy stops working, adding a drug that blocks the PI3K/AKT pathway to fulvestrant can delay progression. Alpelisib helped women whose tumours carry a PIK3CA mutation; capivasertib helped overall, most clearly when the pathway was altered; inavolisib with palbociclib and fulvestrant lengthened survival in PIK3CA-mutated disease. Gedatolisib helped in tumours without the mutation.

    After endocrine therapy: SOLAR-1 (PIK3CA-mutated, n=341): PFS 11.0 vs 5.7 months, HR 0.65 (0.50-0.85); final OS HR 0.86 (0.64-1.15), not significant. CAPItello-291 (N=708): PFS HR 0.60; altered pathway HR 0.50. INAVO120 (N=325, endocrine-resistant, PIK3CA-mutated): PFS 15.0 vs 7.3 months, OS HR 0.67 (0.48-0.94). VIKTORIA-1 (PIK3CA wild-type, N=392): PFS HR 0.24 and 0.33 vs fulvestrant.

  190. 2019 · Treatment · Chronic lymphocytic leukaemia

    CLL14: fixed-duration venetoclax-obinutuzumab for comorbid patients

    CLL14 tested a one-year course of venetoclax plus obinutuzumab against chlorambucil plus obinutuzumab in people with untreated CLL and other health conditions. After two years, about nine in ten on venetoclax-obinutuzumab were free of progression, versus about six in ten. The US regulator approved the combination in May 2019.

    CLL14 (open-label phase 3; 432 randomised, 216 per group; CIRS score above 6 or creatinine clearance below 70 ml/min): 12 cycles of venetoclax with 6 of obinutuzumab vs chlorambucil-obinutuzumab. Investigator-assessed PFS at median 28.1 months: HR 0.35 (95% CI 0.23 to 0.53; P<0.001); 24-month PFS 88.2% vs 64.1%. At 6 years: median PFS 76.2 vs 36.4 months (HR 0.40); OS 78.7% vs 69.2% (HR 0.69, 95% CI 0.48 to 1.01; P=0.052).

  191. 2019 · Treatment · Chronic lymphocytic leukaemia

    Acalabrutinib: ELEVATE-TN, ASCEND, ELEVATE-RR

    Acalabrutinib is an oral BTK inhibitor tested in three randomised trials: untreated CLL against chemotherapy plus an antibody, relapsed CLL against two standard regimens, and head-to-head with ibrutinib. Progression-free survival was longer than with the comparators in the first two and similar to ibrutinib in the third. The US regulator approved it for CLL in 2019.

    ELEVATE-TN (n=535, untreated): 24-month PFS 93% acalabrutinib-obinutuzumab and 87% acalabrutinib vs 47% obinutuzumab-chlorambucil; HR 0.1 and 0.20. ASCEND (n=310, relapsed/refractory): median PFS not reached vs 16.5 months, HR 0.31. ELEVATE-RR (n=533, del(17p) or del(11q)): noninferior to ibrutinib, median PFS 38.4 months in both arms, HR 1.00 (0.79 to 1.27).

  192. 2019 · Treatment · Colorectal cancer

    BEACON: encorafenib plus cetuximab for BRAF V600E mCRC

    Some bowel cancers carry a change called BRAF V600E and do poorly on standard chemotherapy. In a randomised trial of people whose cancer had progressed after one or two earlier treatments, adding encorafenib to cetuximab lengthened survival by several months. The US regulator approved the two-drug version, not the three-drug one tested alongside it.

    Open-label phase 3 trial, 665 patients with BRAF V600E-mutated metastatic colorectal cancer after one or two prior regimens, randomised 1:1:1 to triplet (encorafenib, binimetinib, cetuximab), doublet (encorafenib, cetuximab) or control (cetuximab with irinotecan or FOLFIRI). Interim median OS 9.0 vs 5.4 months, triplet vs control (HR 0.52, 95% CI 0.39-0.70); doublet 8.4 months (HR 0.60, 95% CI 0.45-0.79). Confirmed ORR 26% vs 2%.

  193. 2019 · Reversal · Endometrial cancer

    GOG-258: adding radiotherapy to chemotherapy did not extend RFS

    In stage III or IVA endometrial cancer, chemotherapy plus radiotherapy was compared with chemotherapy alone after surgery. Women given both did not stay free of relapse longer. Radiotherapy lowered recurrence in the vagina and in pelvic and para-aortic lymph nodes, but cancer returned at distant sites more often. Final overall survival results also showed no difference.

    Randomised phase 3 (813 enrolled; 736 eligible for the primary analysis), stage III or IVA: cisplatin with volume-directed radiation then carboplatin-paclitaxel (chemoradiotherapy) vs carboplatin-paclitaxel alone. 60-month RFS 59% (95% CI 53-65) vs 58% (53-64); HR 0.90 (90% CI 0.74-1.10). 5-year vaginal recurrence 2% vs 7%; pelvic or para-aortic nodal 11% vs 20%; distant 27% vs 21%. Final OS (median follow-up 112 months): HR 1.05 (95% CI 0.82-1.34; p=0.72).

  194. 2019 · Treatment · Endometrial cancer

    Lenvatinib plus pembrolizumab after platinum: KEYNOTE-146 and -775

    After platinum-based chemotherapy, people with advanced endometrial cancer received lenvatinib plus pembrolizumab or doxorubicin or paclitaxel chemotherapy. Cancer took longer to progress and survival was longer with the combination, but severe side effects were more common. A US approval in 2019 rested on an earlier single-group study; the randomised trial was published in 2022.

    Phase 3, open-label (N=827; 697 pMMR): lenvatinib 20 mg plus pembrolizumab 200 mg vs doxorubicin or paclitaxel after one platinum regimen. pMMR: median PFS 6.6 vs 3.8 months (HR 0.60; 95% CI 0.50-0.72); median OS 17.4 vs 12.0 months (HR 0.68; 0.56-0.84). All-comers OS HR 0.62 (0.51-0.75). Grade 3 or higher adverse events 88.9% vs 72.7%. Earlier single-arm study (N=108): ORR at week 24 38.0%.

  195. 2019 · Treatment · Gastric and gastro-oesophageal junction cancer

    FLOT4: perioperative FLOT versus ECF/ECX in gastric and GEJ cancer

    A German trial compared two chemotherapy combinations given before and after surgery for stomach or junction cancer. The docetaxel-containing combination, FLOT, was associated with longer survival than the older ECF or ECX combination, and serious side effects occurred at a similar rate in both groups.

    FLOT4 (phase 2/3; 716 patients with cT2 or higher and/or node-positive resectable gastric or GEJ adenocarcinoma) compared perioperative FLOT with ECF/ECX. Phase 3, primary endpoint OS (ITT): median 50 vs 35 months, HR 0.77 (95% CI 0.63-0.94). Phase 2 pathological complete regression (TRG1a): 16% vs 6% (p=0.02). Related serious adverse events 27% in both groups.

  196. 2019 · Treatment · Glioblastoma

    Lomustine plus temozolomide in MGMT-methylated glioblastoma (CeTeG)

    A 2019 trial in Germany of 141 people with newly diagnosed glioblastoma and a methylated MGMT promoter compared standard temozolomide chemoradiation with radiotherapy plus lomustine and temozolomide. Median survival was about 31 months with standard treatment and 48 months with the combination, a result the authors call suggestive and interpret with caution because the trial was small.

    CeTeG/NOA-09 (open-label phase 3; 141 randomised, 129 in modified ITT; MGMT-methylated, age 18-70): median OS 31.4 months (95% CI 27.7-47.1) with temozolomide chemoradiation vs 48.1 months (32.6-not assessable) with lomustine-temozolomide; HR 0.60 (95% CI 0.35-1.03); log-rank p=0.0492. Grade 3 or higher adverse events 51% vs 59%. Authors advise caution owing to small size.

  197. 2019 · Understanding · Head and neck cancer

    ORATOR: transoral robotic surgery vs radiotherapy, oropharynx

    A small randomised trial compared radiation with transoral robotic surgery plus neck dissection for early throat cancer. Swallowing-related quality of life one year later was somewhat better after radiation, though the authors said the difference was not clinically meaningful. At five years there were no differences in survival, and side effects differed in pattern.

    ORATOR (phase 2, N=68, 34 per arm; T1-T2, N0-2 oropharyngeal squamous cell carcinoma): radiotherapy (with chemotherapy if N1-2) vs transoral robotic surgery plus neck dissection. Primary endpoint, swallowing quality of life (MDADI) at 1 year: mean 86.9 (SD 11.4) vs 80.1 (13.0), P = 0.042; authors judged the difference not clinically meaningful. Final results (median follow-up 5.1 years): MDADI scores converged, grade 2-5 adverse events 91% (radiotherapy) vs 97% (TORS plus neck dissection), P = 0.61, no differences in OS or PFS.

  198. 2019 · Treatment · Head and neck cancer

    KEYNOTE-048: pembrolizumab first line, recurrent or metastatic

    Adults whose head and neck cancer had returned or spread, and who had not yet been treated for it, received pembrolizumab alone, pembrolizumab with chemotherapy, or cetuximab with chemotherapy. Median survival was 13.0 months with pembrolizumab plus chemotherapy against 10.7 months with cetuximab plus chemotherapy; pembrolizumab alone improved survival in people whose tumours expressed PD-L1.

    Randomised open-label phase 3 (1:1:1; N=882): untreated recurrent or metastatic HNSCC; pembrolizumab, pembrolizumab plus platinum-5-FU, or cetuximab plus platinum-5-FU. Median OS, pembrolizumab plus chemotherapy vs control, total population: 13.0 vs 10.7 months (HR 0.77; 95% CI 0.63-0.93). Pembrolizumab alone, CPS 1 or more: 12.3 vs 10.3 months (HR 0.78; 95% CI 0.64-0.96). Neither regimen improved PFS at the second interim analysis.

  199. 2019 · Treatment · Hepatocellular carcinoma

    REACH-2: ramucirumab in AFP-selected patients after sorafenib

    Ramucirumab was compared with placebo in 292 people with advanced liver cancer who had received sorafenib and whose blood alpha-fetoprotein (AFP) was high (400 ng/mL or more). Median survival was 8.5 months with ramucirumab and 7.3 months with placebo. An earlier trial without the AFP requirement did not show a significant survival difference.

    REACH-2 (double-blind phase 3, 2:1, ITT N=292, AFP of 400 ng/mL or more, prior sorafenib): ramucirumab (n=197) vs placebo (n=95), median OS 8.5 vs 7.3 months, HR 0.710 (95% CI 0.531-0.949; P=0.0199); median PFS 2.8 vs 1.6 months, HR 0.452 (95% CI 0.339-0.603). REACH (N=565, no AFP threshold): median OS 9.2 vs 7.6 months, HR 0.87 (95% CI 0.72-1.05; P=0.14).

  200. 2019 · De-escalation · Hodgkin lymphoma

    GHSG HD16 and HD17: PET-guided radiotherapy in early stages

    Two trials of the German Hodgkin Study Group tested leaving out radiotherapy after a negative PET scan. In early favourable disease (HD16), progression-free survival was lower without radiotherapy, and the authors said radiotherapy cannot be omitted without clinically relevant loss of control. In early unfavourable disease (HD17), after a different chemotherapy sequence, omission was judged possible.

    HD16 (Fuchs 2019): PET-2-negative, per-protocol (628), 5-year PFS 93.4% with CMT vs 86.1% with ABVD alone (HR 1.78, 95% CI 1.02-3.12); 2024 follow-up, median 64 months: HR 2.05 (1.20-3.51). HD17 (Borchmann 2021): 1100 patients, 2 eBEACOPP + 2 ABVD, 5-year PFS 97.3% standard vs 95.1% PET4-guided; difference 2.2% (95% CI -0.9 to 5.3), margin 8%. Different risk groups and PET rules.

  201. 2019 · Treatment · Kidney cancer (renal cell carcinoma)

    KEYNOTE-426: pembrolizumab plus axitinib versus sunitinib (2019)

    In untreated advanced clear cell kidney cancer, pembrolizumab plus axitinib was compared with sunitinib. At the first planned analysis, more people were alive at 12 months, the cancer took longer to progress and more tumours shrank. Follow-up has continued beyond five years. The FDA approved the combination in April 2019.

    KEYNOTE-426 (phase 3, n=861, ITT): pembrolizumab plus axitinib vs sunitinib. First interim analysis (median follow-up 12.8 months): 12-month OS 89.9% vs 78.3%, HR 0.53 (95% CI 0.38-0.74); median PFS 15.1 vs 11.1 months, HR 0.69 (0.57-0.84); ORR 59.3% vs 35.7%. At 30.6 months: OS HR 0.68 (0.55-0.85). With at least 5 years of follow-up: OS HR 0.84 (0.71-0.99). FDA approval 19 April 2019.

  202. 2019 · Reversal · Non-Hodgkin lymphoma (DLBCL and follicular)

    DA-EPOCH-R not better than R-CHOP: CALGB/Alliance 50303 (2019)

    In a US intergroup trial, 491 eligible adults with previously untreated diffuse large B-cell lymphoma received either R-CHOP or the more intensive infusional regimen DA-EPOCH-R. Progression-free and overall survival did not differ significantly. DA-EPOCH-R was more toxic, with more severe nerve damage (19 in 100 people versus 3 in 100).

    Alliance/CALGB 50303 (phase III, six cycles each): 524 registered, 491 eligible in the final analysis. Median follow-up 5 years: PFS HR 0.93 (95% CI 0.68-1.27; P=.65), 2-year PFS 78.9% (DA-EPOCH-R) vs 75.5% (R-CHOP); OS HR 1.09 (0.75-1.59; P=.64), 2-year OS 86.5% vs 85.7%. Grade 3-4 febrile neutropenia 35.0% vs 17.7%; neuropathy 18.6% vs 3.3%. Treatment-related deaths 2.1% in each arm.

  203. 2019 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    Polatuzumab vedotin with bendamustine-rituximab: FDA 2019

    In a small randomised study of people with relapsed or refractory diffuse large B-cell lymphoma who could not have a stem-cell transplant, adding polatuzumab vedotin to bendamustine and rituximab raised the complete response rate from about 18 in 100 to 40 in 100. The FDA granted accelerated approval in June 2019.

    GO29365 randomised phase 2 cohort (80 patients, 40 per arm) in transplantation-ineligible relapsed or refractory DLBCL, pola-BR vs BR. IRC-assessed complete response at end of treatment (primary): 40.0% vs 17.5% (P=.026). Median PFS 9.5 vs 3.7 months (HR 0.36, 95% CI 0.21 to 0.63); median OS 12.4 vs 4.7 months (HR 0.42, 0.24 to 0.75; median follow-up 22.3 months). Pola-BG single-arm cohort (n=27): CR 29.6%.

  204. 2019 · Treatment · Melanoma

    E1609: adjuvant ipilimumab versus high-dose interferon (2019)

    In a large trial after surgery for high-risk melanoma, ipilimumab at a lower dose (3 mg/kg) was linked to longer overall survival than high-dose interferon, with fewer serious side effects. The approved higher dose (10 mg/kg) was not shown to be better than interferon, and more patients stopped it because of side effects.

    Phase 3, three arms; resected AJCC-7 stage IIIB, IIIC, M1a or M1b melanoma (N=1,670): ipilimumab 3 mg/kg (n=523), high-dose interferon alfa-2b (n=636), ipilimumab 10 mg/kg (n=511). Ipilimumab 3 mg/kg vs interferon (n=1,051, concurrent randomisation): OS HR 0.78 (95.6% repeated CI 0.61-0.99; P=0.044); RFS HR 0.85 (99.4% CI 0.66-1.09; P=0.065). Ipilimumab 10 mg/kg vs interferon did not reach significance.

  205. 2019 · Treatment · Multiple myeloma

    Quadruplet induction before transplant: CASSIOPEIA, GRIFFIN, PERSEUS

    In people with newly diagnosed myeloma who could have a stem-cell transplant, three trials added daratumumab to the multi-drug regimens given before and after transplant. The proportion with the deepest responses rose in each, and the trial with progression as its main outcome found a lower risk of progression or death.

    Daratumumab added around ASCT. CASSIOPEIA (D-VTd, n=1085): sCR at day 100 29% versus 20%, OR 1.60 (95% CI 1.21 to 2.12). GRIFFIN (D-RVd, n=207, registered phase 2): sCR 42.4% versus 32.0% at the primary analysis. PERSEUS (D-VRd, n=709): 48-month PFS 84.3% versus 67.7%, HR 0.42 (0.30 to 0.59); MRD negativity 75.2% versus 47.5%.

  206. 2019 · Treatment · Multiple myeloma

    Isatuximab: ICARIA-MM, IKEMA, HD7 and IMROZ

    Isatuximab is a second antibody against CD38. Added to pomalidomide or carfilzomib regimens at relapse, it lengthened time without progression. In newly diagnosed myeloma it raised the share with undetectable residual disease before transplant and, in people not having a transplant, lowered the risk of progression or death.

    Isatuximab, randomised phase 3. ICARIA-MM (Isa-Pd versus Pd, n=307): median PFS 11.5 versus 6.5 months, HR 0.596 (95% CI 0.44 to 0.81). IKEMA (Isa-Kd versus Kd, n=302): HR 0.53 (99% CI 0.32 to 0.89). GMMG-HD7 part 1 (n=660): MRD negativity after induction 50% versus 36%. IMROZ (Isa-VRd versus VRd, n=446): 60-month PFS 63.2% versus 45.2%, HR 0.60 (98.5% CI 0.41 to 0.88).

  207. 2019 · Treatment · Neuroblastoma and Wilms tumour

    Tandem vs single autologous transplant in high-risk neuroblastoma

    In a randomized trial, children and young adults with high-risk neuroblastoma given two stem-cell transplants were more often free of relapse, progression, a second cancer or death at three years than those who had one: about six in ten against about five in ten. Only about half of eligible patients were randomized, so results may not generalize.

    COG ANBL0532 (phase 3, 142 centres): 652 eligible patients aged up to 30 years, 355 randomized to tandem transplant (thiotepa/cyclophosphamide, then dose-reduced carboplatin/etoposide/melphalan; n=176) or single transplant (carboplatin/etoposide/melphalan; n=179). 3-year EFS from randomization 61.6% (95% CI 54.3 to 68.9) vs 48.4% (41.0 to 55.7); one-sided log-rank P=0.006. The authors note the low randomization rate.

  208. 2019 · Reversal · Ovarian cancer

    GOG-252: IP regimens plus bevacizumab, no significant PFS gain

    In 1,560 women with newly diagnosed advanced ovarian cancer, all given bevacizumab, intraperitoneal carboplatin or cisplatin regimens did not significantly lengthen progression-free survival compared with intravenous carboplatin. Median progression-free survival was about 25 months with intravenous treatment and 26 to 27 months with the two intraperitoneal regimens.

    GOG-252 (N=1560, 84.8 months follow-up; bevacizumab in all arms): median PFS 24.9 (IV carboplatin), 27.4 (IP carboplatin), 26.2 months (IP cisplatin); HR vs IV 0.925 (95% CI 0.802-1.07) and 0.977 (0.847-1.13), not significant. Stage II/III, residual 1 cm or less (n=1380): 26.9, 28.7, 27.8. Median OS, same order: 75.5, 78.9, 72.9. FACT-O Trial Outcome Index worse with IP cisplatin during chemotherapy.

  209. 2019 · Treatment · Ovarian cancer

    PRIMA: first-line niraparib maintenance beyond BRCA

    PRIMA tested niraparib or placebo as maintenance after first-line chemotherapy in people at high risk of recurrence, whatever their tumour's HRD status. Progression-free survival was longer with niraparib, with the largest gain in HRD-positive tumours. Final survival results, after about six years of follow-up, showed no difference between the groups.

    PRIMA (N=733, 2:1): median PFS 21.9 vs 10.4 months in HRD tumours (HR 0.43, 95% CI 0.31-0.59) and 13.8 vs 8.2 months overall (HR 0.62, 0.50-0.76). Final OS after a median follow-up of 73.9 months: HR 1.01 (0.84-1.23) overall and 0.95 (0.70-1.29) in HRd; 37.8% of placebo and 11.7% of niraparib patients later received a PARP inhibitor.

  210. 2019 · Treatment · Ovarian cancer

    PAOLA-1: olaparib plus bevacizumab maintenance, HRD-positive disease

    PAOLA-1 added olaparib to bevacizumab maintenance after first-line chemotherapy. Progression-free survival was longer overall, with the largest gain, about twenty months in the median, in HRD-positive tumours. Overall survival was not clearly longer in everyone, but an exploratory analysis in the HRD-positive group favoured olaparib.

    PAOLA-1 (N=806; all received bevacizumab): median PFS 22.1 vs 16.6 months, HR 0.59 (95% CI 0.49-0.72); HRD-positive 37.2 vs 17.7 months, HR 0.33 (0.25-0.45). Final OS: ITT 56.5 vs 51.6 months, HR 0.92 (0.76-1.12); exploratory HRD-positive HR 0.62 (0.45-0.85), 5-year OS 65.5% vs 48.4%.

  211. 2019 · De-escalation · Ovarian cancer

    LION: lymphadenectomy not linked to longer survival

    In 2019 a randomised trial of 647 women with advanced ovarian cancer, whose visible tumour had been completely removed and whose lymph nodes looked normal, compared removing the pelvic and para-aortic lymph nodes with leaving them in place. Survival was not longer with node removal, and serious complications were more frequent.

    LION: 647 randomised intraoperatively (FIGO IIB to IV, macroscopically complete resection, normal nodes before and during surgery). Median overall survival 69.2 months without lymphadenectomy versus 65.5 months with it (hazard ratio for death with lymphadenectomy 1.06, 95% CI 0.83 to 1.34; P=0.65); median progression-free survival 25.5 months in both groups (hazard ratio 1.11, 0.92 to 1.34). Repeat laparotomy 12.4% vs 6.5%; mortality within 60 days 3.1% vs 0.9% (with vs without lymphadenectomy).

  212. 2019 · Treatment · Ovarian cancer

    Secondary cytoreduction at first relapse: GOG-213, SOC-1, DESKTOP III

    Three randomised trials asked whether operating at the first relapse, before platinum chemotherapy, helps women whose cancer returned at least six months after platinum treatment. DESKTOP III and SOC-1, which chose patients by scoring systems, reported longer survival or longer progression-free survival; GOG-213, which used investigators' judgement, found no survival gain.

    Platinum-sensitive first relapse, surgery plus chemotherapy versus chemotherapy alone. DESKTOP III (407 patients): median OS 53.7 vs 46.0 months, HR 0.75 (95% CI 0.59 to 0.96). SOC-1 (357): median PFS 17.4 vs 11.9 months, HR 0.58 (0.45 to 0.74); interim OS HR 0.82 (0.57 to 1.19). GOG-213 (485): median OS 50.6 vs 64.7 months, HR 1.29 (0.97 to 1.72).

  213. 2019 · Treatment · Pancreatic cancer

    POLO: maintenance olaparib for germline BRCA-mutated disease

    In 154 people with spread pancreatic cancer and an inherited BRCA change whose disease had not worsened on platinum chemotherapy, the pill olaparib held the cancer back for a median of about 7 months versus about 4 months with placebo. The final analysis found no clear survival difference.

    POLO, double-blind phase 3: 154 patients with germline BRCA1/2-mutated metastatic pancreatic cancer, no progression on first-line platinum; maintenance olaparib (92) vs placebo (62). Median PFS (BICR) 7.4 vs 3.8 months, HR 0.53 (95% CI 0.35-0.82; P=0.004). Final OS 19.0 vs 19.2 months, HR 0.83 (0.56-1.22; P=.3487); estimated 3-year survival 33.9% vs 17.8%.

  214. 2019 · Treatment · Prostate cancer

    AR inhibitors with ADT, hormone-sensitive (TITAN, ARCHES, ENZAMET)

    In 2019 three trials, TITAN, ARCHES and ENZAMET, added an androgen-receptor inhibitor to hormone therapy for metastatic hormone-sensitive prostate cancer, each against its own control. All three reported longer survival without progression or longer overall survival. In TITAN, 82.4% of men on apalutamide were alive at two years, against 73.5% on placebo.

    TITAN (n=1052; apalutamide versus placebo, plus ADT): 24-month rPFS 68.2% versus 47.5% (HR 0.48; 95% CI 0.39-0.60), interim OS HR 0.67 (0.51-0.89), final OS HR 0.65 (0.53-0.79). ARCHES (n=1150; enzalutamide versus placebo): rPFS HR 0.39 (0.30-0.50); final OS HR 0.66 (0.53-0.81). ENZAMET (n=1125; open-label; control a standard antiandrogen): OS HR 0.67 (0.52-0.86); planned analysis HR 0.70 (0.58-0.84).

  215. 2019 · Reversal · Sarcoma and GIST

    Olaratumab: phase 2 survival benefit not confirmed in ANNOUNCE

    A randomised phase 2 trial in 133 people reported median survival of 26.5 months with olaratumab plus doxorubicin versus 14.7 months with doxorubicin alone, and the drug received US accelerated approval in 2016. The phase 3 ANNOUNCE trial in 509 people found no difference (20.4 versus 19.7 months), and the European authorisation was revoked in 2019.

    Phase 2 (N=133 randomised): median OS 26.5 vs 14.7 months (HR 0.46; 95% CI 0.30-0.71); PFS HR 0.67 (95% CI 0.44-1.02; p=0.0615). Phase 3 ANNOUNCE (N=509; doxorubicin plus olaratumab vs plus placebo): median OS 20.4 vs 19.7 months (HR 1.05; 95% CI 0.84-1.30; p=.69); leiomyosarcoma 21.6 vs 21.9 (HR 0.95). FDA accelerated approval 19 October 2016; EC revocation 22 July 2019; FDA withdrawal listed 25 February 2020.

  216. 2019 · Detection · Testicular germ cell tumors

    Prospective study of serum miR-371a-3p in testicular GCT

    In 2019 a multicentre study measured a small RNA molecule, microRNA-371a-3p, in the blood of 616 men with testicular germ cell tumours and 258 male controls. The test outperformed the established blood markers, and the marker was expressed in all tumour types except teratoma. The authors called for further validation before clinical implementation.

    Dieckmann KP et al., J Clin Oncol 2019: prospective multicentre study, 616 patients with testicular GCT (359 seminoma, 257 nonseminoma) and 258 male controls; serum miR-371a-3p by qPCR (M371 test). Primary diagnosis, preoperative samples from 522 patients vs controls: sensitivity 90.1%, specificity 94.0%, AUC 0.966; PPV 97.2% (four institutions). AFP, β-hCG and LDH sensitivities were below 50% in seminoma. Teratoma did not express the marker. Authors: consider after further validation.