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Bending the Curve Trial by Trial
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2020 to today

Precision & engineered

Visual dialect: glass, clean light, high-precision data viz. Eras are a storytelling frame, not a historical claim.

  1. 2020 · Treatment · Acute myeloid leukaemia (including APL)

    QUAZAR: oral azacitidine maintenance after first remission

    In 2020 the US approved azacitidine tablets to continue treatment for adults with AML in a first remission after intensive chemotherapy who cannot complete intensive curative therapy. In the QUAZAR trial, median survival was about 25 months with the tablets and about 15 months with placebo.

    QUAZAR AML-001: randomized, double-blind, placebo-controlled phase 3 of oral azacitidine (CC-486 300 mg, 14 days per 28-day cycle) vs placebo in AML in first remission, aged 55 or older, not transplant candidates (n=472; 238 vs 234). Median OS from randomization 24.7 vs 14.8 months (P<0.001); median RFS 10.2 vs 4.8 months (P<0.001). CC-486 is not bioequivalent to injectable azacitidine.

  2. 2020 · Treatment · Bladder cancer

    JAVELIN Bladder 100: avelumab maintenance after chemotherapy

    In 700 people whose advanced bladder cancer had not progressed after first-line platinum chemotherapy, adding avelumab maintenance to supportive care was linked to median survival of about 21 months compared with about 14 months with supportive care alone.

    Phase 3 (N=700): maintenance avelumab plus best supportive care vs best supportive care alone after four to six cycles of gemcitabine with cisplatin or carboplatin. Median OS 21.4 vs 14.3 months (HR 0.69; 95% CI 0.56-0.86; P=0.001); 1-year OS 71.3% vs 58.4%. PD-L1-positive tumours: HR 0.56 (95% CI 0.40-0.79). Grade 3 or higher adverse events 47.4% vs 25.2%.

  3. 2020 · Treatment · Bladder cancer

    KEYNOTE-057: pembrolizumab for BCG-unresponsive CIS

    In a single-group study of people whose carcinoma in situ no longer responded to BCG and who could not or chose not to have the bladder removed, pembrolizumab, an immune checkpoint inhibitor, led to a complete response at three months in about two in five. US regulators approved it for this group in January 2020.

    Phase 2 single-arm cohort A (101 enrolled): pembrolizumab 200 mg every 3 weeks for up to 24 months in BCG-unresponsive CIS, ineligible for or declining cystectomy. Complete response at 3 months 41% (39/96; 95% CI 30.7 to 51.1) in the efficacy population; median follow-up 36.4 months. Grade 3 or 4 treatment-related adverse events 13%. FDA supplement approval 8 January 2020.

  4. 2020 · Treatment · Bladder cancer

    Nadofaragene firadenovec for BCG-unresponsive NMIBC

    Nadofaragene firadenovec is a gene therapy placed in the bladder that delivers instructions for making interferon alfa-2b. In a single-group study of people whose cancer no longer responded to BCG, just over half of those with carcinoma in situ had a complete response; fewer than half of these held at one year. The US approved it in December 2022.

    Phase 3 single-arm study (157 enrolled, 33 US centres): intravesical nadofaragene firadenovec, repeated at months 3, 6 and 9 if no high-grade recurrence. Per-protocol CIS cohort: complete response within 3 months 53.4% (55/103); maintained at 12 months in 25 of 55 (45.5%); null hypothesis CR below 27%. FDA BLA approval 16 December 2022 (CBER).

  5. 2020 · Treatment · Breast cancer

    Adjuvant CDK4/6 inhibition: monarchE and NATALEE

    Two trials showed that adding a CDK4/6 inhibitor to hormone therapy after surgery lowers the chance of recurrence in higher-risk hormone-receptor-positive breast cancer. Abemaciclib was given for two years in node-positive disease, and ribociclib for three years in a wider stage two and three group. After seven years abemaciclib has also shown a small survival gain.

    monarchE (N=5637, node-positive, high risk, open-label): iDFS HR 0.75 (0.60-0.93) at the first analysis; at 7 years iDFS 77.4% vs 70.9% (HR 0.734) and OS HR 0.842 (0.722-0.981; P=0.027), 7-year OS 86.8% vs 85.0%. NATALEE (N=5101, stage II-III): 3-year iDFS 90.7% vs 87.6%, HR 0.749 (0.628-0.892); overall survival immature.

  6. 2020 · Treatment · Breast cancer

    KEYNOTE-522: pembrolizumab added to chemotherapy in early TNBC

    Adding the immunotherapy drug pembrolizumab to chemotherapy before surgery, and continuing it afterwards, left more people with early triple-negative breast cancer with no invasive cancer at surgery. Later reports showed fewer relapses and longer survival. The immune drug also adds its own side effects.

    Phase 3, randomised 2:1, placebo-controlled; stage II or III TNBC (N=1174; 784 vs 390): neoadjuvant pembrolizumab with paclitaxel-carboplatin then anthracycline-cyclophosphamide, adjuvant pembrolizumab up to nine cycles. pCR 64.8% vs 51.2% (first 602 patients; P<0.001). EFS at 36 months 84.5% vs 76.8% (HR 0.63; 95% CI 0.48-0.82). OS at 60 months 86.6% vs 81.7% (P = 0.002; no HR in the abstract).

  7. 2020 · Treatment · Breast cancer

    Sacituzumab govitecan (ASCENT): first TROP-2 ADC in metastatic TNBC

    In people whose triple-negative breast cancer had spread and come back after earlier treatment, a drug that carries chemotherapy directly to cancer cells (sacituzumab govitecan) was compared with standard single-agent chemotherapy. It roughly tripled the time before the cancer grew and extended life. Low blood counts and diarrhea were more common.

    Phase 3, relapsed or refractory metastatic TNBC; sacituzumab govitecan vs single-agent chemotherapy of physician's choice, 1:1. Primary analysis (235 vs 233 without brain metastases): median PFS 5.6 vs 1.7 months (HR 0.41; 95% CI 0.32-0.52; P<0.001); median OS 12.1 vs 6.7 months (HR 0.48; 95% CI 0.38-0.59); ORR 35% vs 5%. Final analysis (ITT, 267 vs 262): PFS 4.8 vs 1.7 months (HR 0.41); OS 11.8 vs 6.9 months (HR 0.51; 95% CI 0.42-0.63).

  8. 2020 · Understanding · Cervical cancer

    WHO 2020 global strategy to eliminate cervical cancer

    In November 2020 the World Health Organization published a global strategy to eliminate cervical cancer as a public health problem. It sets 2030 targets for vaccination, screening and treatment, and a threshold of 4 per 100,000 women-years for elimination. A modelling study in poorer countries explored how vaccination and screening could get there.

    WHO global strategy (publication page dated November 2020): by 2030, 90% of girls fully vaccinated against HPV by age 15, 70% of women screened with a high-performance test by age 35 and again by 45, and 90% of women with cervical disease treated; elimination threshold 4 per 100,000 women-years. Brisson 2020 (modelling, 78 low- and lower-middle-income countries): girls-only vaccination was predicted to reduce median incidence from 19.8 to 2.1 per 100,000 women-years over the next century.

  9. 2020 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Inotuzumab ozogamicin for relapsed paediatric CD22+ ALL

    Inotuzumab ozogamicin is an antibody joined to a cell-killing drug that targets CD22 on leukemia cells. In a European phase 1 study, four in five heavily pretreated children responded after the first course; a Children's Oncology Group study reported remission in about three in five. The FDA approved it for children aged 1 year and older in March 2024.

    Single-arm studies. ITCC-059 phase 1 (25 patients): overall response after course 1 80% (95% CI 59 to 93), 84% of responders MRD-negative complete response, 12-month OS 40% (95% CI 25 to 66). COG AALL1621 phase 2 (48 evaluable, ages 1 to 21): CR/CRi 58.3% (90% CI 46.5 to 69.3). FDA label, 6 March 2024, ITCC-059 analysis of 53 patients: CR 22 of 53 (42%; 95% CI 28.1 to 55.9).

  10. 2020 · Reversal · Chronic lymphocytic leukaemia

    Early treatment of asymptomatic CLL: FCR (CLL7), ibrutinib (CLL12)

    Two randomised trials tested treating early-stage CLL before symptoms appear, one with chemoimmunotherapy and one with ibrutinib. Both reported longer event-free survival with early treatment, but neither showed longer overall survival. The authors of both concluded that watching and waiting should remain the standard.

    CLL7 (800 enrolled; 201 high-risk patients randomised to FCR, n=100, or watch and wait, n=101): median EFS not reached vs 18.5 months (P<0.001); 5-year OS 82.9% vs 79.9% (P=0.864). CLL12 (n=363; ibrutinib 182, placebo 181): median EFS not reached vs 47.8 months, HR 0.25 (95% CI 0.14 to 0.43) at 31 months; final analysis: no survival benefit at median observation 69.3 months, 26 deaths; 5-year survival 93.3% vs 93.6%.

  11. 2020 · Treatment · Colorectal cancer

    KEYNOTE-177: pembrolizumab first-line for MSI-H/dMMR metastatic CRC

    In untreated advanced MSI-H/dMMR bowel cancer (tumours that cannot repair DNA copying errors), pembrolizumab was compared with chemotherapy. Cancer progressed after a median of 16.5 versus 8.2 months, with fewer severe side effects. At over five years median survival was 77.5 versus 36.7 months, but the final survival analysis was not statistically significant and many chemotherapy patients later received immunotherapy.

    Open-label phase 3: 307 patients with untreated MSI-H/dMMR metastatic CRC randomised 1:1 to pembrolizumab (n=153) or investigator-choice chemotherapy (n=154), crossover allowed. PFS median 16.5 vs 8.2 months (HR 0.60, 95% CI 0.45 to 0.80; P=0.0002; second interim analysis). Final OS HR 0.74 (95% CI 0.53 to 1.03; p=0.036), prespecified significance not met. At over 5 years, OS HR 0.73 (95% CI 0.53 to 0.99); effective crossover 62%. FDA approval 29 June 2020.

  12. 2020 · Treatment · Colorectal cancer

    Total neoadjuvant therapy: RAPIDO and PRODIGE 23

    Two randomised trials gave chemotherapy before surgery for locally advanced rectal cancer, rather than only after it. In RAPIDO, a week of radiotherapy then chemotherapy lowered treatment failure at three years; in PRODIGE 23, chemotherapy before chemoradiotherapy improved disease-free survival. In RAPIDO, cancer returned locally more often at five years after complete surgery.

    RAPIDO (920 randomised): short-course radiotherapy then chemotherapy vs chemoradiotherapy; 3-year disease-related treatment failure 23.7% vs 30.4% (HR 0.75, 95% CI 0.60-0.95); at 5.6 years locoregional recurrence after R0/R1 resection 10% vs 6% (P=0.027). PRODIGE 23 (n=461): FOLFIRINOX before chemoradiotherapy; 3-year DFS 76% vs 69% (HR 0.69, 0.49-0.97); 7-year overall survival 81.9% vs 76.1% (RMST P=0.033). Endpoints, populations and controls differ.

  13. 2020 · Treatment · Endometrial cancer

    GARNET: dostarlimab in recurrent dMMR endometrial cancer

    In a single-group study, people whose endometrial cancer had a mismatch repair deficiency and had progressed after platinum chemotherapy received dostarlimab alone. About four in ten had a confirmed tumour response, and most responses were lasting at the time of the report. There was no comparison group.

    Open-label single-group GARNET cohort A1: dostarlimab 500 mg every 3 weeks for 4 doses, then 1000 mg every 6 weeks, in dMMR endometrial cancer after platinum chemotherapy (104 treated; 71 evaluable). Confirmed ORR by blinded central review 42.3% (95% CI 30.6-54.6); 12.7% complete and 29.6% partial responses. Median DOR not reached at 11.2 months median follow-up; response maintained 96.4% at 6 and 76.8% at 12 months.

  14. 2020 · Treatment · Gastric and gastro-oesophageal junction cancer

    Trastuzumab deruxtecan in HER2-positive gastric cancer

    In 2020 a randomised phase 2 trial reported that trastuzumab deruxtecan, an antibody linked to a chemotherapy drug, shrank tumours in about half of people with HER2-positive stomach cancer previously treated with trastuzumab, versus about one in seven with chemotherapy. A 2025 phase 3 trial reported longer survival than ramucirumab plus paclitaxel.

    DESTINY-Gastric01 (phase 2, 2:1, 187 treated, prior trastuzumab): ORR 51% vs 14% (P<0.001); median OS 12.5 vs 8.4 months, HR 0.59 (95% CI 0.39 to 0.88), P=0.01. DESTINY-Gastric04 (phase 3, 494 randomised, second line): median OS 14.7 vs 11.4 months vs ramucirumab plus paclitaxel, HR 0.70 (0.55 to 0.90), P=0.004; ILD or pneumonitis 13.9% vs 1.3%.

  15. 2020 · Reversal · Glioblastoma

    Nivolumab phase 3 trials in glioblastoma do not meet their endpoints

    Three randomised phase 3 trials tested the immunotherapy nivolumab in glioblastoma: one at first recurrence and two alongside first-line radiotherapy. In none did people live longer with nivolumab. In one first-line trial, those given temozolomide with radiotherapy lived longer than those given nivolumab with radiotherapy.

    CheckMate 143 (recurrent, n=369): nivolumab vs bevacizumab, median OS 9.8 vs 10.0 months, HR 1.04 (95% CI 0.83 to 1.30). CheckMate 498 (MGMT-unmethylated, n=560): nivolumab plus radiotherapy vs temozolomide plus radiotherapy, median OS 13.4 vs 14.9 months, HR 1.31 (95% CI 1.09 to 1.58). CheckMate 548 (MGMT-methylated or indeterminate, n=716): median OS 28.9 vs 32.1 months, HR 1.1.

  16. 2020 · De-escalation · Head and neck cancer

    Sentinel-node strategy vs neck dissection in early oral cancer

    In operable early oral and oropharyngeal cancer, patients were randomly assigned to neck dissection or to a sentinel node biopsy, with neck dissection only if the sentinel node held cancer. Neck recurrence-free survival at two years was about 90 percent with both approaches, and functional outcomes were better with the sentinel approach during the first six months.

    Phase 3 equivalence trial, 307 randomised, T1-T2 N0 operable oral or oropharyngeal cancer; 279 analysable (139 neck dissection, 140 sentinel node). Neck node recurrence-free survival at 2 years 89.6% with dissection vs 90.7% with the sentinel strategy (equivalence P<.01). 5-year RFS and 2- and 5-year DSS and OS were not significantly different. Median hospital stay 8 vs 7 days (P<.01); functional outcomes worse after dissection up to 6 months.

  17. 2020 · Treatment · Hepatocellular carcinoma

    IMbrave150: atezolizumab plus bevacizumab versus sorafenib

    In 501 people with advanced liver cancer who had not had drug treatment, atezolizumab plus bevacizumab was compared with sorafenib. About two-thirds were alive at 12 months with the combination, against about half with sorafenib (67% versus 55%). Median time without progression was 6.8 versus 4.3 months. The FDA approved the combination in May 2020.

    IMbrave150 (open-label phase 3, 2:1, ITT N=501, no prior systemic therapy): atezolizumab plus bevacizumab (n=336) vs sorafenib (n=165). Primary analysis: OS HR 0.58 (95% CI 0.42-0.79; P<0.001), 12-month OS 67.2% vs 54.6%; median PFS 6.8 vs 4.3 months (HR 0.59; 95% CI 0.47-0.76). Post hoc update (median follow-up 15.6 months): median OS 19.2 vs 13.4 months, HR 0.66 (95% CI 0.52-0.85).

  18. 2020 · Treatment · Lung cancer

    ADAURA: adjuvant osimertinib after resection

    After surgery to remove an EGFR-mutated lung cancer, three years of osimertinib kept the cancer from returning or causing death far more often than placebo. At two years, 89 in 100 people on osimertinib were alive and disease-free, against 52 in 100 on placebo, and five-year survival was also higher.

    ADAURA (N=682; osimertinib 339, placebo 343), completely resected EGFR-mutated stage IB-IIIA NSCLC, double-blind, 3 years of treatment. Stage II-IIIA (primary): 24-month DFS 90% vs 44%, HR 0.17 (99.06% CI 0.11-0.26). Stage IB-IIIA: 89% vs 52%, HR 0.20 (99.12% CI 0.14-0.30). Final OS, stage IB-IIIA: 5-year OS 88% vs 78%, HR 0.49 (95.03% CI 0.34-0.70).

  19. 2020 · Treatment · Lung cancer

    CROWN: lorlatinib first-line, long follow-up

    CROWN randomly compared lorlatinib with crizotinib as first treatment for ALK-positive lung cancer. After one year, 78 in 100 people on lorlatinib and 39 in 100 on crizotinib were alive without progression. After five years, 60 in 100 on lorlatinib and 8 in 100 on crizotinib remained progression-free (investigator-assessed).

    CROWN (N=296; lorlatinib 149, crizotinib 147), untreated advanced ALK-positive NSCLC. Planned interim (BICR): 12-month PFS 78% vs 39%, HR 0.28 (0.19-0.41). Unplanned 3-year update (BICR): crizotinib median PFS 9.3 months, 3-year PFS 64% vs 19%, HR 0.27. Post hoc 5-year update (investigator): 5-year PFS 60% vs 8%, HR 0.19 (0.13-0.27); lorlatinib median not reached.

  20. 2020 · Treatment · Lung cancer

    RET fusion-positive NSCLC: selpercatinib and pralsetinib

    RET gene fusions are found in about 1 to 2 in 100 lung cancers. In single-arm studies the oral RET inhibitors selpercatinib and pralsetinib shrank tumours in roughly six in ten previously treated people and in 70 to 85 in 100 untreated people. A later randomised trial found that first-line selpercatinib delayed progression compared with chemotherapy, with or without pembrolizumab.

    Single-arm phase 1-2 studies in RET fusion-positive NSCLC. Selpercatinib: ORR 64% (95% CI 54-73) in 105 platinum-pretreated patients, 85% (70-94) in 39 untreated. Pralsetinib: ORR 61% (50-71; n=87) pretreated, 70% (50-86; n=27) untreated. Randomised LIBRETTO-431, first line, ITT-pembrolizumab population (n=212): median PFS 24.8 vs 11.2 months, HR 0.46 (0.31-0.70), P<0.001.

  21. 2020 · Treatment · Lung cancer

    MET exon 14 skipping: capmatinib and tepotinib

    About 3 to 4 in 100 lung cancers have a MET exon 14 skipping mutation. In single-arm studies, capmatinib and tepotinib shrank tumours in about four to seven in ten people, depending on earlier treatment and how response was assessed. The FDA granted accelerated approval in 2020 and 2021 and later converted both to full approval.

    Single-arm phase 2 studies in MET exon 14 skipping NSCLC. Capmatinib (GEOMETRY mono-1): ORR 41% (95% CI 29-53; n=69, one or two prior lines) and 68% (48-84; n=28, untreated); median DOR 9.7 and 12.6 months. Tepotinib (VISION): independent-review ORR 46% (36-57) among 99 patients with at least 9 months of follow-up, median DOR 11.1 months; investigator-assessed ORR 56% (45-66).

  22. 2020 · Detection · Lung cancer

    NELSON: volume-CT screening and lung-cancer mortality

    The Dutch-Belgian NELSON trial randomly assigned about 13,000 men aged 50 to 74 to four CT screens over several years or to no screening. After at least ten years, lung cancer deaths were about a quarter lower in the screened group. Results in the smaller group of women were less certain.

    Randomised trial, Netherlands and Belgium: 13,195 men (primary analysis) aged 50-74 were assigned to volume-CT screening at baseline, years 1, 3 and 5.5, or no screening; minimum follow-up 10 years. Lung-cancer mortality was 2.50 vs 3.30 deaths per 1000 person-years; cumulative rate ratio at 10 years 0.76 (95% CI 0.61-0.94; P=0.01). In 2594 women (subgroup), rate ratio 0.67 (0.38-1.14). Adherence 90.0%; suspicious-nodule referral rate 2.1%.

  23. 2020 · Treatment · Lung cancer

    Lurbinectedin in SCLC: 2020 approval, IMforte, 2026 withdrawal

    Lurbinectedin received US accelerated approval in 2020 for small-cell lung cancer that progressed after platinum chemotherapy, based on a single-arm study in which about 35 in 100 people responded. In 2025 it was approved with atezolizumab as maintenance after first-line treatment, after a randomised trial. In 2026 the 2020 indication was withdrawn at the sponsor's request.

    Single-arm phase 2 basket (SCLC cohort, N=105): investigator-assessed ORR 35.2% (95% CI 26.2-45.2); accelerated approval 15 June 2020. ATLANTIS (phase 3, N=613, lurbinectedin 2.0 mg/m2 plus doxorubicin vs topotecan or CAV): median OS 8.6 vs 7.6 months (HR 0.97; 0.82-1.15). IMforte (N=483 randomised after induction): IRF PFS HR 0.54 (0.43-0.67); OS HR 0.73 (0.57-0.95; P=0.017). FDA recorded the sponsor's voluntary withdrawal of the 2020 indication on 30 September 2026.

  24. 2020 · Reversal · Multiple myeloma

    Venetoclax in myeloma: BELLINI signals harm, CANOVA misses PFS

    Venetoclax blocks BCL-2, a protein that helps some myeloma cells survive. In an unselected group with relapsed myeloma, adding it to bortezomib and dexamethasone delayed progression but was followed by more deaths, mostly from infection. A later trial in people whose myeloma has a t(11;14) change did not reach its progression-free survival goal.

    BELLINI (venetoclax or placebo plus Vd, n=291): median PFS 22.4 versus 11.5 months, HR 0.63 (95% CI 0.44 to 0.90); eight fatal infections with venetoclax, none with placebo. Final analysis at 45.6 months: OS HR 1.19 (0.80 to 1.77; P=0.39). CANOVA (venetoclax-dexamethasone versus Pd, t(11;14)-positive, n=263): median PFS 9.9 versus 5.8 months, HR 0.823 (0.596 to 1.136; P=0.24), primary end point not met; OS HR 0.856 (0.612 to 1.197).

  25. 2020 · Treatment · Neuroblastoma and Wilms tumour

    Naxitamab: accelerated approval for relapsed or refractory disease

    In November 2020 the US regulator granted accelerated approval to naxitamab, an anti-GD2 antibody given with GM-CSF, for relapsed or refractory high-risk neuroblastoma in bone or bone marrow. A later report from one of the supporting single-arm studies found about half of 52 evaluable patients responded. Approval depends on a confirmatory trial, still listed as ongoing in October 2026.

    FDA accelerated approval (21 CFR 601.41) on 25 November 2020; postmarketing requirement 3950-1 asks for a trial enrolling at least 80 patients with evaluable disease. Trial 201, which its authors cite as one of two single-arm studies supporting the approval (interim analysis after the approval, data cutoff 31 December 2021, efficacy population 52): ORR 50% (95% CI 36 to 64), CR 38%, PR 12%; 1-year PFS 35% (16 to 54); 1-year OS 93% (80 to 98).

  26. 2020 · Treatment · Pancreatic cancer

    PREOPANC: preoperative chemoradiotherapy versus immediate surgery

    PREOPANC randomised people with resectable or borderline resectable pancreatic cancer to chemoradiotherapy before surgery or surgery first. The 2020 report found no clear survival gain: median 16.0 against 14.3 months. A 2022 analysis of the same trial with longer follow-up reported better survival, with about 20 in 100 alive at five years against 6.5 in 100.

    PREOPANC (Versteijne 2020, 2022): 246 eligible patients, resectable or borderline resectable PDAC, preoperative gemcitabine chemoradiotherapy then surgery vs immediate surgery, both with adjuvant gemcitabine. 2020 (primary, ITT): median OS 16.0 vs 14.3 months, HR 0.78 (95% CI 0.58-1.05, P=.096); R0 resection 71% vs 40%. 2022 (59 months): HR 0.73 (0.56-0.96, P=.025); 5-year OS 20.5% vs 6.5%.

  27. 2020 · Treatment · Prostate cancer

    PARP inhibitors for HRR-altered mCRPC (PROfound, TRITON)

    Some prostate cancers carry changes in DNA-repair genes such as BRCA2. After a hormonal drug stopped working, olaparib (PROfound) and rucaparib (TRITON3) delayed progression compared with the control drugs in men whose tumours had those changes: about 7 versus 4 months with olaparib. Olaparib also lengthened survival in the BRCA1, BRCA2 and ATM group.

    PROfound (phase 3, N=387; progression on enzalutamide or abiraterone, HRR alteration): cohort A (BRCA1, BRCA2 or ATM) imaging-based PFS 7.4 vs 3.6 months (HR 0.34; 95% CI 0.25-0.47); final OS 19.1 vs 14.7 months (HR 0.69; 0.50-0.97), 66% of controls crossing over. TRITON3 (phase 3, N=405): BRCA subgroup rPFS 11.2 vs 6.4 months (HR 0.50; 0.36-0.69). TRITON2 (phase 2): BRCA ORR 43.5% by independent review.

  28. 2020 · Detection · Prostate cancer

    PSMA PET-CT before curative-intent treatment (proPSMA)

    A 2020 Australian randomised study compared two ways of staging men with high-risk prostate cancer before surgery or radiotherapy: CT with a bone scan, or PSMA PET-CT. PSMA PET-CT was more accurate at finding spread to pelvic lymph nodes or distant sites, and management changed more often. The report gives imaging accuracy, not survival.

    proPSMA (302 randomised, ten Australian hospitals, high-risk localised disease): accuracy for pelvic nodal or distant metastasis 92% (95% CI 88-95) with gallium-68 PSMA-11 PET-CT vs 65% (60-69) with CT plus bone scan (difference 27%, 95% CI 23-31; p<0.0001). Sensitivity 85% vs 38%; specificity 98% vs 91%. First-line imaging changed management in 28% (PSMA PET-CT) vs 15% (conventional) (p=0.008). Primary endpoint was accuracy; no survival data.

  29. 2020 · Treatment · Sarcoma and GIST

    Avapritinib (PDGFRA exon 18) and ripretinib (fourth line)

    In 2020 the US regulator approved two GIST drugs. Avapritinib, for PDGFRA exon 18 mutations, was tested in a single-arm phase 1 study in which 49 of 56 people with the D842V mutation had a response. Ripretinib, after three or more kinase inhibitors, was tested against placebo: median progression-free survival 6.3 versus 1.0 months.

    NAVIGATOR (phase 1, open-label), PDGFRA D842V-mutant GIST: overall response 88% (95% CI 76-95), 49 of 56 patients, 5 complete and 44 partial responses; recommended phase 2 dose 300 mg. INVICTUS (phase 3, 129 patients, 2:1, ripretinib 150 mg daily vs placebo): median PFS by BICR 6.3 months (95% CI 4.6-6.9) vs 1.0 (0.9-1.7), HR 0.15 (0.09-0.25), p<0.0001. FDA approvals 9 January and 15 May 2020.

  30. 2020 · Reversal · Sarcoma and GIST

    STRASS: preoperative radiotherapy in retroperitoneal sarcoma

    In 266 adults with a newly diagnosed retroperitoneal sarcoma that could be operated on, adding radiotherapy before surgery did not lengthen the time free of abdominal recurrence: median 4.5 years with radiotherapy plus surgery and 5.0 years with surgery alone. The authors concluded that preoperative radiotherapy should not be standard.

    Open-label phase 3 (EORTC-62092 STRASS; N=266; 133 per arm, 1:1): preoperative radiotherapy (50.4 Gy in 28 fractions) plus surgery vs surgery alone. Median follow-up 43.1 months. Median abdominal recurrence-free survival (primary, ITT) 4.5 vs 5.0 years (HR 1.01; 95% CI 0.71-1.44; log-rank p=0.95). Grade 3-4 lymphopenia 77% vs 1%; serious adverse events 24% vs 10%.

  31. 2020 · Treatment · Thyroid cancer

    Selpercatinib in RET-altered thyroid cancer (LIBRETTO-001)

    About seven in ten medullary thyroid cancers carry a change in the RET gene, and a few other thyroid cancers carry a RET fusion. In a single-arm study, the RET-targeted pill selpercatinib shrank tumours in roughly 70 to 80 of every 100 people treated, including people who had already tried other drugs.

    LIBRETTO-001, phase 1-2, single-arm; primary endpoint ORR by independent review. RET-mutant MTC after vandetanib or cabozantinib: ORR 69% (95% CI 55-81), 1-year PFS 82% (69-90), 55 patients. Vandetanib/cabozantinib-naive: ORR 73% (62-82), 1-year PFS 92% (82-97), 88 patients. Previously treated RET fusion-positive thyroid cancer: ORR 79% (54-94), 19 patients. Update (cutoff 13 January 2023): ORR 82.5% (143 naive MTC), 77.6% (152 pretreated MTC).

  32. 2021 · Reversal · Bladder cancer

    Atezolizumab and durvalumab urothelial indications withdrawn

    Between 2021 and 2022 the US FDA removed three accelerated approvals for PD-L1 inhibitors in bladder cancer: durvalumab and atezolizumab after platinum chemotherapy, and atezolizumab for people who could not have cisplatin. They had been granted on response-rate data. In the randomised IMvigor211 trial, survival did not differ significantly in the first group tested, people with higher PD-L1.

    FDA accelerated approvals: durvalumab 1 May 2017 (removal letter 19 Feb 2021); atezolizumab post-platinum 18 May 2016 (removal 13 Apr 2021); atezolizumab cisplatin-ineligible 17 Apr 2017 (removal 2 Dec 2022). IMvigor211 (N=931): OS in the PD-L1 IC2/3 group 11.1 vs 10.6 months (HR 0.87; 95% CI 0.63-1.21; P=0.41). IMvigor210 cohort 2: ORR 15% overall.

  33. 2021 · Treatment · Bladder cancer

    CheckMate 274: adjuvant nivolumab after radical surgery

    After surgery for high-risk muscle-invasive urothelial cancer, up to a year of nivolumab was compared with placebo. Median time free of disease was about 21 months with nivolumab and 11 months with placebo. Severe (grade 3 or higher) treatment-related side effects were more frequent with nivolumab. The FDA approved adjuvant nivolumab in August 2021.

    CheckMate 274 (phase 3, double-blind, n=709): adjuvant nivolumab 240 mg every 2 weeks for up to 1 year vs placebo after radical surgery. ITT median DFS 20.8 vs 10.8 months; 6-month DFS 74.9% vs 60.3%; HR 0.70 (98.22% CI 0.55-0.90, P<0.001). PD-L1 1% or more: 6-month 74.5% vs 55.7%, HR 0.55 (98.72% CI 0.35-0.85). Grade 3 or higher treatment-related adverse events 17.9% vs 7.2%. FDA approval 19 August 2021.

  34. 2021 · Treatment · Breast cancer

    OlympiA: one year of adjuvant olaparib for germline BRCA carriers

    For people with an inherited BRCA1 or BRCA2 variant and early HER2-negative breast cancer at high risk of coming back, one year of the PARP inhibitor olaparib after standard treatment left more people alive and free of invasive cancer at three years than placebo. Longer follow-up also showed a survival advantage.

    Double-blind phase 3 (N=1836): HER2-negative high-risk early breast cancer with germline BRCA1/2 pathogenic or likely pathogenic variants, after local treatment and (neo)adjuvant chemotherapy; 1 year olaparib vs placebo. First interim analysis (median follow-up 2.5 years): 3-year iDFS 85.9% vs 77.1% (HR 0.58; P<0.001). Second interim OS analysis (3.5 years): HR 0.68 (98.5% CI 0.47-0.97; P = 0.009); 4-year OS 89.8% vs 86.4%.

  35. 2021 · Reversal · Breast cancer

    Atezolizumab in PD-L1+ metastatic TNBC: approval, then withdrawal

    In 2019 the US regulator gave early approval to atezolizumab with nab-paclitaxel for advanced triple-negative breast cancer with PD-L1 on immune cells, based on delayed progression. A second trial, using paclitaxel, did not show a benefit, and the indication was removed in October 2021. A different immunotherapy combination stayed approved for a differently defined group.

    IMpassion130 (N=902; atezolizumab plus nab-paclitaxel): PD-L1-positive subgroup median PFS 7.5 vs 5.0 months (HR 0.62; 95% CI 0.49-0.78); ITT PFS 7.2 vs 5.5 months (HR 0.80); final ITT OS HR 0.87 (95% CI 0.75-1.02; P = 0.077). IMpassion131 (N=651; paclitaxel; PD-L1-positive): PFS 6.0 vs 5.7 months (HR 0.82; 95% CI 0.60-1.12; P = 0.20); OS HR 1.11. An FDA letter of 6 October 2021 approved removal of the indication.

  36. 2021 · Understanding · Cervical cancer

    HPV vaccination programme in England and cervical cancer incidence

    England began offering HPV vaccine to girls in 2008. Registry analyses found much lower rates of cervical cancer and of the precancer called CIN3 in young women who were offered the vaccine at age 12 to 13, and smaller reductions in those offered it later as teenagers. These are observational findings, not a trial.

    Register-based age-period-cohort analyses, England (Lancet 2021, to June 2019; BMJ 2024 update to June 2020). Lancet, women aged 20 to under 30 years: relative reduction in cervical cancer rates vs the unvaccinated reference cohort 87% (95% CI 72-94) if the bivalent vaccine was offered at age 12-13 (from September 2008), 62% at 14-16, 34% at 16-18; CIN3 reductions 97%, 75%, 39%. BMJ, 12-13 cohort, added 12 months: cancer 83.9% (63.8-92.8) and CIN3 94.3% (92.6-95.7) lower.

  37. 2021 · De-escalation · Cervical cancer

    Fewer HPV vaccine doses: India, KEN SHE and ESCUDDO (2021-2025)

    Three studies asked whether fewer HPV vaccine doses protect as well. A cohort in India, a randomised trial in Kenya and a large randomised trial (ESCUDDO) each reported high protection from one dose against lasting HPV 16 and 18 infection; India and ESCUDDO compared one dose with two or three. The measure was infection, not cancer.

    Endpoint: persistent HPV 16/18 infection, not cancer. India (cohorts after a trial of two vs three doses; single-dose group non-randomised): vaccine efficacy 95.4% (95% CI 85.0-99.9) single dose, 93.1% two doses, 93.3% three doses. KEN SHE (randomised vs meningococcal vaccine, 18 months): 97.5% for bivalent (81.6-99.7) and for nonavalent (81.7-99.7). ESCUDDO: one dose noninferior to two; bivalent rate difference -0.13 per 100 (95% CI -0.45 to 0.15).

  38. 2021 · Treatment · Cervical cancer

    KEYNOTE-826: pembrolizumab added to first-line chemotherapy

    In 617 people with cervical cancer that had spread, persisted or returned, adding the immune checkpoint drug pembrolizumab to first-line chemotherapy was compared with adding placebo. Cancer took longer to grow, and in the final analysis median survival was about 29 versus 17 months in people whose tumours expressed PD-L1.

    Phase 3, double-blind, placebo-controlled (N=617); pembrolizumab 200 mg every 3 weeks plus platinum chemotherapy, with or without bevacizumab. First interim analysis, CPS 1 or more (n=548): median PFS 10.4 vs 8.2 months (HR 0.62; 95% CI 0.50-0.77). Final analysis, CPS 1 or more: median OS 28.6 vs 16.5 months (HR 0.60; 95% CI 0.49-0.74). FDA approval for CPS 1 or more on 13 October 2021.

  39. 2021 · Treatment · Cervical cancer

    Tisotumab vedotin: accelerated approval 2021, then innovaTV 301

    Tisotumab vedotin is an antibody joined to a chemotherapy drug. In a single-arm study of 101 treated people whose cervical cancer had progressed, about one in four had a confirmed response. A randomised trial later found median survival of 11.5 versus 9.5 months compared with chemotherapy, and US approval changed from accelerated to regular.

    innovaTV 204 (phase 2, single-arm): confirmed ORR 24% (95% CI 16-33) by independent review; FDA accelerated approval 20 September 2021. innovaTV 301 (phase 3, N=502, versus investigator-choice chemotherapy): median OS 11.5 vs 9.5 months (HR 0.70; 95% CI 0.54-0.89; P=0.004); median PFS 4.2 vs 2.9 months (HR 0.67). FDA regular approval 29 April 2024; EU authorisation 28 March 2025.

  40. 2021 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Blinatumomab versus chemotherapy in first relapse of B-ALL

    Two randomized trials published in 2021 compared the antibody blinatumomab with chemotherapy given before stem cell transplant in children and young adults with first relapse of B-cell leukemia. The trial in high-risk children stopped early because blinatumomab did better. The larger trial, which included intermediate-risk patients, stopped early with no statistically significant difference in disease-free survival.

    Two phase 3 RCTs (JAMA, 2021). Amgen high-risk first-relapse trial, children (108 randomized; one blinatumomab cycle before transplant): EFS HR 0.33 (95% CI 0.18 to 0.61), events 31% vs 57%; stopped early for benefit. COG AALL1331, ages 1 to 30 (208 randomized; two cycles): 2-year DFS 54.4% vs 39.0%, HR 0.70 (95% CI 0.47 to 1.03), 1-sided P=.03 against a threshold of .025; terminated early.

  41. 2021 · De-escalation · Childhood acute lymphoblastic leukemia (ALL)

    Fewer vincristine and dexamethasone pulses in standard risk

    In a Children's Oncology Group trial, 2,364 average-risk children with standard-risk B-cell ALL were randomly given vincristine and dexamethasone pulses every 4 or every 12 weeks during maintenance. Five-year disease-free survival was about 94 in 100 versus 95 in 100, with no significant difference. A higher methotrexate starting dose did not help.

    COG AALL0932: 9,229 NCI standard-risk B-ALL patients enrolled; 2,364 average-risk patients randomised (2 x 2) at the start of maintenance. Vincristine/dexamethasone every 4 versus 12 weeks: 5-year DFS 94.1% versus 95.1% (P=.86), OS 98.3% versus 98.6% (P=.69). Methotrexate starting dose 20 versus 40 mg/m2: DFS 95.1% versus 94.2% (P=.92), OS 98.8% versus 98.1% (P=.89). All eligible patients (9,226): 5-year EFS 92.0%, OS 96.8%.

  42. 2021 · Reversal · Chronic lymphocytic leukaemia

    PI3K inhibitors: CLL approvals, lymphoma indications withdrawn

    Two PI3K-blocking drugs, idelalisib and duvelisib, delayed progression in randomised trials of relapsed CLL and were approved in the US in 2014 and 2018. Their accelerated approvals for lymphoma uses were later withdrawn, in 2021 and 2022, and the February 2022 idelalisib label restricts how it is combined and used.

    Idelalisib-rituximab vs placebo-rituximab (n=220, relapsed CLL with coexisting conditions; stopped early at first interim analysis): median PFS 5.5 months with placebo, not reached with idelalisib, HR 0.15; ORR 81% vs 13%; 12-month OS 92% vs 80%. DUO (n=319, duvelisib vs ofatumumab): median PFS 13.3 vs 9.9 months, HR 0.52; ORR 74% vs 45%. FDA withdrew accelerated lymphoma indications on 17 December 2021 and 18 February 2022.

  43. 2021 · Treatment · Chronic myeloid leukemia

    Asciminib approved after ASCEMBL versus bosutinib

    In 2021 a trial of 233 people with CML who had already taken two or more TKIs compared asciminib, which acts at a different site on BCR-ABL1, with bosutinib. At 24 weeks about one in four on asciminib and about one in eight on bosutinib had a major molecular response. The FDA granted accelerated approval in October 2021.

    ASCEMBL (NCT03106779): open-label phase 3, 233 patients with CML-CP after 2 or more TKIs, asciminib 40 mg twice daily vs bosutinib 500 mg once daily (2:1). MMR at week 24: 25.5% vs 13.2% (adjusted difference 12.2%, 95% CI 2.19-22.30; P=.029). Week 96: 37.6% vs 15.8% (difference 21.7%, 95% CI 10.53-32.95). Grade 3 or higher adverse events 50.6% vs 60.5% at the primary analysis. FDA accelerated approval 29 October 2021.

  44. 2021 · Reversal · Colorectal cancer

    PRODIGE 7: HIPEC added to cytoreductive surgery (peritoneal CRC)

    PRODIGE 7 randomly assigned 265 people with colorectal cancer that had spread to the lining of the abdomen to surgery that removes all visible tumour, with or without heated chemotherapy washed through the abdomen. Median survival was about forty-one to forty-two months in both groups, and later complications were more frequent with the heated chemotherapy.

    PRODIGE 7 (Quénet 2021): phase 3, 265 patients with colorectal peritoneal metastases (PCI 25 or less) after complete cytoreduction, randomised to surgery plus oxaliplatin HIPEC (n=133) or surgery alone (n=132). Median OS 41.7 months (95% CI 36.2-53.8) vs 41.2 (35.1-49.7); HR 1.00 (95.37% CI 0.63-1.58), P=0.99; median follow-up 63.8 months. Grade 3 or worse adverse events at 60 days: 26% vs 15% (P=0.035).

  45. 2021 · Treatment · Gastric and gastro-oesophageal junction cancer

    First-line PD-1 plus chemotherapy in HER2-negative gastric cancer

    From 2021, trials adding a PD-1 immune checkpoint inhibitor to first-line chemotherapy reported longer survival in advanced HER2-negative stomach and junction cancers, with larger estimated benefit at higher PD-L1 scores. An East Asian trial improved progression-free but not overall survival. In 2025 US labels narrowed to PD-L1-positive tumours.

    Phase 3 trials of a PD-1 inhibitor added to first-line chemotherapy, HER2-negative disease. CheckMate 649, PD-L1 CPS 5 or more: OS HR 0.71 (98.4% CI 0.59 to 0.86). KEYNOTE-859, ITT: median OS 12.9 vs 11.5 months, HR 0.78 (95% CI 0.70 to 0.87). RATIONALE-305, TAP score 5% or more: 17.2 vs 12.6 months, HR 0.74. ATTRACTION-4 (Asia): OS HR 0.90 (95% CI 0.75 to 1.08).

  46. 2021 · Treatment · Gastric and gastro-oesophageal junction cancer

    KEYNOTE-811: pembrolizumab plus trastuzumab and chemotherapy

    In 2021 the US regulator approved pembrolizumab with trastuzumab and chemotherapy for HER2-positive stomach cancer based on tumour response: about three in four patients responded, versus about one in two when placebo was added instead. Later survival data, with the benefit mainly in PD-L1-positive tumours, led to a full approval in 2025 limited to those tumours.

    KEYNOTE-811 (phase 3, double-blind). First interim analysis (264 patients): ORR 74.4% vs 51.9%, P=0.00006 (FDA accelerated approval 5 May 2021). Later interim analyses (698 patients): PFS HR 0.72 (95% CI 0.60 to 0.87); OS HR 0.87 then 0.84, not significant. Final OS (ITT, FDA authors' summary): median 20.0 vs 16.8 months, HR 0.80 (0.67 to 0.94); CPS 1 or more HR 0.79, CPS below 1 HR 1.10.

  47. 2021 · Treatment · Glioblastoma

    Dabrafenib plus trametinib for BRAF V600E-mutant glioma

    In a single-arm trial of adults with BRAF V600E-mutant brain tumours that had returned or progressed, about one in three people with high-grade glioma and about seven in ten with low-grade glioma had a tumour response to dabrafenib plus trametinib. US approvals followed in 2022 and 2023.

    ROAR basket trial, single-arm phase 2, adults with recurrent or progressive BRAF V600E-mutant glioma (interim analysis 16, cutoff 14 September 2020): investigator-assessed ORR 33% (95% CI 20 to 49; 15 of 45) in the high-grade cohort, which included 31 with glioblastoma, and 69% (95% CI 39 to 91; 9 of 13) in the low-grade cohort. Randomised phase 2 in paediatric low-grade glioma: response 47% vs 11% with chemotherapy.

  48. 2021 · Reversal · Head and neck cancer

    Four add-ons to definitive head and neck treatment show no benefit

    Four large trials added a new drug to standard treatment for head and neck cancer that had not spread widely: avelumab, pembrolizumab or xevinapant during chemoradiotherapy, or atezolizumab afterwards. None improved the main outcome, and with xevinapant the results were worse than with placebo.

    Four randomised phase 3 trials (N=697, 804, 406, 730) in locally advanced SCCHN. Avelumab plus chemoradiotherapy: PFS HR 1.21 (95% CI 0.93-1.57). Pembrolizumab plus chemoradiotherapy: EFS HR 0.83 (95% CI 0.68-1.03). Adjuvant atezolizumab: EFS HR 0.94 (95% CI 0.70-1.26). Xevinapant plus chemoradiotherapy: EFS HR 1.33 (95% CI 1.05-1.67); OS HR 1.39 (95% CI 1.04-1.86). Results are not pooled.

  49. 2021 · Treatment · Head and neck cancer

    PD-1 antibodies added to gemcitabine-cisplatin in first-line NPC

    In three trials in Asia, people with nasopharyngeal cancer that had returned or spread received gemcitabine and cisplatin with either a PD-1 immune drug or placebo. In each trial the cancer took longer to grow with the immune drug; in the toripalimab trial the median was 21.4 months at final analysis, compared with 8.2 months with placebo.

    Three double-blind phase 3 trials, same gemcitabine-cisplatin backbone vs placebo, first-line recurrent or metastatic NPC. Primary-analysis PFS HR (independent review): toripalimab 0.52 (95% CI 0.36-0.74; N=289), camrelizumab 0.54 (95% CI 0.39-0.76; N=263), tislelizumab 0.52 (95% CI 0.38-0.73; N=263). JUPITER-02 final OS HR 0.63 (95% CI 0.45-0.89). CAPTAIN-1st 5-year OS 37.8% vs 24.2% (HR 0.74). FDA approved toripalimab 27 October 2023 and penpulimab 23 April 2025.

  50. 2021 · Reversal · Hepatocellular carcinoma

    CheckMate 459 and withdrawal of nivolumab's HCC indication

    In 743 people with advanced liver cancer who had not had drug treatment, nivolumab did not reach its prespecified significance level for overall survival against sorafenib (median 16.4 versus 14.7 months). The single-agent nivolumab indication after sorafenib, accelerated in 2017, appears on the FDA's withdrawn list with a date of 23 July 2021.

    CheckMate 459 (open-label phase 3, ITT N=743, first-line): nivolumab (n=371) vs sorafenib (n=372), median OS 16.4 vs 14.7 months, HR 0.85 (95% CI 0.72-1.02; P=0.075); protocol-defined significance level P=0.0419 not reached; median follow-up 15.2 and 13.4 months. FDA list: single-agent nivolumab for hepatocellular carcinoma after sorafenib, accelerated approval 22 September 2017, withdrawal 23 July 2021; no reason stated.

  51. 2021 · Treatment · Kidney cancer (renal cell carcinoma)

    Belzutifan for VHL disease-associated tumours (LITESPARK-004)

    Belzutifan, a tablet that blocks a protein called HIF-2 alpha, was tested in people with von Hippel-Lindau disease, an inherited condition with a high risk of kidney cancer. About half of the participants had a measurable kidney tumour response in the first report, and about two thirds at roughly four years of follow-up. The FDA approved it in August 2021.

    LITESPARK-004 (single-arm phase 2, 61 patients with VHL disease-associated RCC): belzutifan 120 mg daily; ORR 49% (95% CI 36-62) at median follow-up 21.8 months by independent review. At 49.9 months, ORR 67% (95% CI 54-79), complete responses 11%; grade 3 treatment-related events 18%, none grade 4-5. FDA approval 13 August 2021 for VHL disease needing therapy for RCC, CNS haemangioblastomas or pNET.

  52. 2021 · Treatment · Kidney cancer (renal cell carcinoma)

    CLEAR: lenvatinib plus pembrolizumab versus sunitinib (2021)

    In untreated advanced kidney cancer, lenvatinib plus pembrolizumab and lenvatinib plus everolimus were each compared with sunitinib. The cancer took about 15 months longer to progress with lenvatinib plus pembrolizumab, and the risk of death was lower in the first report and in the final survival analysis. The FDA approved this combination in August 2021.

    CLEAR (phase 3, n=1069): lenvatinib plus pembrolizumab vs sunitinib: median PFS 23.9 vs 9.2 months, HR 0.39 (95% CI 0.32-0.49); OS HR 0.66 (0.49-0.88). Lenvatinib plus everolimus: median PFS 14.7 months, HR 0.65 (0.53-0.80); OS HR 1.15 (0.88-1.50). Final OS (cutoff 31 July 2022): HR 0.79 (0.63-0.99); medians 53.7 vs 54.3 months. FDA approval of the pembrolizumab combination 10 August 2021.

  53. 2021 · Treatment · Kidney cancer (renal cell carcinoma)

    CheckMate 9ER: nivolumab plus cabozantinib versus sunitinib (2021)

    In untreated advanced clear cell kidney cancer, nivolumab plus cabozantinib was compared with sunitinib. Cancer took about twice as long to progress (16.6 versus 8.3 months), more tumours shrank, and survival was longer in the first report and in the final analysis. The FDA approved the combination in January 2021.

    CheckMate 9ER (phase 3, open-label, 651 randomised, ITT): nivolumab 240 mg every 2 weeks plus cabozantinib 40 mg daily vs sunitinib. Median PFS 16.6 vs 8.3 months, HR 0.51 (95% CI 0.41-0.64); 12-month OS 85.7% vs 75.6%, HR 0.60 (98.89% CI 0.40-0.89); ORR 55.7% vs 27.1%. Final OS (median follow-up 32.9 months): median 37.7 vs 34.3 months, HR 0.70 (0.55-0.90). FDA approval 22 January 2021.

  54. 2021 · Treatment · Kidney cancer (renal cell carcinoma)

    KEYNOTE-564: adjuvant pembrolizumab after nephrectomy (2021)

    After kidney cancer surgery, people at high risk of recurrence received the immunotherapy pembrolizumab or a placebo for about a year. About 77 in 100 on pembrolizumab and 68 in 100 on placebo were free of recurrence at two years. A later report found longer overall survival with pembrolizumab. Side effects were more frequent.

    Phase 3, double-blind; clear-cell RCC at high recurrence risk after nephrectomy with or without metastasectomy; pembrolizumab 200 mg every 3 weeks for up to 17 cycles (n=496) vs placebo (n=498). Investigator-assessed DFS at 24 months 77.3% vs 68.1% (HR 0.68; 95% CI 0.53-0.87; P=0.002). Update, median follow-up 57.2 months: OS HR 0.62 (95% CI 0.44-0.87; P=0.005); 48-month OS 91.2% vs 86.0%.

  55. 2021 · Treatment · Lung cancer

    Adjuvant PD-(L)1 after resection: IMpower010 and PEARLS

    After lung cancer surgery, and after chemotherapy where it was given, two trials tested about a year of an immune checkpoint inhibitor against best supportive care or placebo. Both reported longer disease-free survival in their main analyses, but the benefit differed between PD-L1 groups, and the trials differ in design and population.

    IMpower010 (open-label; N=1005 randomised after adjuvant chemotherapy): atezolizumab vs best supportive care; DFS HR 0.66 (95% CI 0.50-0.88) in stage II-IIIA with PD-L1 on at least 1% of tumour cells, 0.79 (0.64-0.96) in all stage II-IIIA, 0.81 (0.67-0.99) in the ITT population. PEARLS/KEYNOTE-091 (triple-blind; N=1177): pembrolizumab vs placebo; DFS HR 0.76 (0.63-0.91) overall; 0.82 (0.57-1.18) with PD-L1 TPS 50% or greater.

  56. 2021 · Treatment · Lung cancer

    KRAS G12C inhibitors: sotorasib and adagrasib

    KRAS G12C is a mutation found in some lung cancers. Two oral drugs, sotorasib and adagrasib, shrank tumours in roughly four in ten people whose cancer had progressed after earlier treatment. Randomised trials against docetaxel reported longer time without progression, though an FDA advisory panel questioned how reliably one trial could be interpreted. Both US approvals are accelerated.

    Single-arm cohorts in previously treated KRAS G12C-mutated NSCLC: sotorasib (CodeBreaK 100, n=126) ORR 37.1%, median DOR 11.1 months, median PFS 6.8 months; adagrasib (KRYSTAL-1, n=116) ORR 42.9%, median PFS 6.5 months. Randomised phase 3 versus docetaxel: sotorasib PFS HR 0.66 (0.51-0.86); adagrasib PFS HR 0.58 (0.45-0.76). Separate trials; not comparable.

  57. 2021 · Treatment · Lung cancer

    HER2-mutant NSCLC: trastuzumab deruxtecan and oral TKIs

    Some lung cancers carry a HER2 mutation, in about 2 to 4 in 100 cases. In single-arm studies, the antibody-drug conjugate trastuzumab deruxtecan shrank tumours in just over half of previously treated people. Two oral drugs, zongertinib and sevabertinib, did so in about two-thirds to three-quarters of people in the main cohorts. US approvals so far are accelerated approvals.

    Single-arm studies in HER2-mutant NSCLC. T-DXd (DESTINY-Lung01, n=91, refractory to standard treatment; 6.4 mg/kg studied): ORR 55% (95% CI 44-65), median PFS 8.2 months; adjudicated drug-related ILD 26%. Zongertinib 120 mg (Beamion LUNG-1): ORR 71% in previously treated cohort 1 (n=75) and 76% in untreated cohort 2 (n=74). Sevabertinib (SOHO-01): ORR 64% (cohort D, n=81) and 71% (cohort F, untreated, n=73).

  58. 2021 · Treatment · Lung cancer

    EGFR exon 20 insertions: amivantamab, CHRYSALIS to PAPILLON

    EGFR exon 20 insertion mutations resist the usual EGFR pills. Amivantamab, an antibody that binds EGFR and MET, shrank tumours in about four in ten people whose cancer had progressed on platinum chemotherapy. Later, adding it to chemotherapy as first treatment delayed progression: median 11.4 months versus 6.7 months with chemotherapy alone.

    CHRYSALIS (phase 1, post-platinum efficacy population, n=81): ORR 40% (95% CI 29-51), median DOR 11.1 months, median PFS 8.3 months. PAPILLON (phase 3, untreated, n=308, 1:1): amivantamab plus carboplatin-pemetrexed vs chemotherapy alone, median PFS 11.4 vs 6.7 months, HR 0.40 (0.30-0.53), P<0.001; ORR 73% vs 47%; interim OS HR 0.67 (0.42-1.09), P=0.11 at 33% maturity.

  59. 2021 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    POLARIX: polatuzumab vedotin with R-CHP vs R-CHOP (2021)

    In a trial of 879 adults with previously untreated, intermediate- or high-risk diffuse large B-cell lymphoma, replacing vincristine in R-CHOP with the antibody-drug conjugate polatuzumab vedotin lowered the risk of progression, relapse or death. After two years, 77 in 100 were free of progression versus 70 in 100. Survival did not differ significantly.

    POLARIX (n=879, double-blind): pola-R-CHP vs R-CHOP. Median follow-up 28.2 months: 2-year PFS 76.7% vs 70.2%, HR 0.73 (95% CI 0.57-0.95; P=0.02); 2-year OS 88.7% vs 88.6% (HR 0.94, 0.65-1.37). Five-year update (median 64.1 months): PFS HR 0.77 (0.62-0.97), 5-year PFS 64.9% vs 59.1%; OS HR 0.85 (0.63-1.15).

  60. 2021 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    ZUMA-7 and TRANSFORM: CAR T cells vs salvage plus transplant

    Two large trials compared CD19 CAR T cells with the usual second-line approach of salvage chemotherapy and, for responders, a stem-cell transplant. People whose lymphoma was resistant to first treatment or returned within a year stayed free of progression or other events for longer with CAR T cells. ZUMA-7 also reported better survival at four years.

    Randomised phase 3 trials in large B-cell lymphoma refractory to or relapsing within 12 months of first-line therapy. ZUMA-7 (n=359): median EFS 8.3 vs 2.0 months, HR 0.40 (95% CI 0.31 to 0.51); 4-year OS 54.6% vs 46.0% (HR 0.73, 0.54 to 0.98). TRANSFORM (n=184, interim): median EFS 10.1 vs 2.3 months, HR 0.35 (0.23 to 0.53). Different CAR T products, eligibility and designs.

  61. 2021 · Reversal · Non-Hodgkin lymphoma (DLBCL and follicular)

    BELINDA: tisagenlecleucel not superior in second line (2021)

    In this randomised trial of tisagenlecleucel CAR T cells against salvage chemotherapy and transplant as second-line treatment for aggressive lymphoma, event-free survival did not differ: the median was 3 months in both groups. The authors concluded that tisagenlecleucel was not superior to standard salvage therapy.

    BELINDA: randomised phase 3, 322 patients with aggressive B-cell lymphoma refractory to or progressing within 12 months of first-line therapy; tisagenlecleucel (optional bridging) vs salvage chemotherapy and autologous HSCT. Median EFS 3.0 months in both groups; HR 1.07 (95% CI 0.82 to 1.40; P=0.61). Response 46.3% vs 42.5%. Authors: tisagenlecleucel was not superior to standard salvage therapy.

  62. 2021 · Reversal · Non-Hodgkin lymphoma (DLBCL and follicular)

    PI3K inhibitors in FL: accelerated approvals withdrawn (2021-2024)

    Four targeted drugs that block the PI3K protein each received accelerated FDA approval for relapsed follicular lymphoma, from 2014 to 2021. Single-arm studies of each drug had reported response rates in indolent lymphoma. All four follicular lymphoma indications were later withdrawn, between December 2021 and March 2024.

    Single-arm phase 2 studies in relapsed or refractory indolent lymphoma reported: idelalisib (n=125; ORR 57%), copanlisib (n=142; ORR 59%), duvelisib (n=129; FL ORR 42.2%), umbralisib (n=208; ORR 47.1%). Each drug received FDA accelerated approval in relapsed FL. Per the FDA list, the FL indications were withdrawn on 17 December 2021 (duvelisib), 18 February 2022 (idelalisib), 31 May 2022 (umbralisib) and 18 March 2024 (copanlisib).

  63. 2021 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    ZUMA-5: axicabtagene ciloleucel in relapsed follicular lymphoma (2021)

    In a single-arm study of people with relapsed follicular or marginal zone lymphoma, nearly all responded to a one-time infusion of their own T cells engineered to target CD19, and about three in four had a complete response. The FDA gave accelerated approval for follicular lymphoma in March 2021; two other CAR T products followed.

    Single-arm phase 2 (ZUMA-5), relapsed or refractory indolent NHL after two or more lines. Primary analysis (n=104; 84 follicular, 20 marginal zone; median follow-up 17.5 months): ORR 92% (95% CI 85 to 97), CR 74%. Three-year report, follicular lymphoma (n=127, median follow-up 41.7 months): ORR 94%, median PFS 40.2 months. ELARA, tisagenlecleucel (n=94 efficacy set): CR rate 69.1%, ORR 86.2%.

  64. 2021 · Treatment · Melanoma

    Adjuvant therapy in stage IIB/IIC: KEYNOTE-716 and CheckMate 76K

    In two separate placebo-controlled phase 3 trials of people with resected stage IIB or IIC melanoma, a year of pembrolizumab (KEYNOTE-716) or nivolumab (CheckMate 76K) was followed by fewer recurrences than placebo at early follow-up. Each trial stands alone, and neither report gives an overall survival result yet.

    Two phase 3 placebo-controlled trials in resected stage IIB/IIC melanoma. KEYNOTE-716 (N=976, 1:1): pembrolizumab vs placebo, RFS HR 0.65 (95% CI 0.46-0.92) at the first interim analysis and 0.61 (95% CI 0.45-0.82) at the second. CheckMate 76K (N=790, 2:1): nivolumab vs placebo, 12-month RFS 89.0% vs 79.4% (HR 0.42; 95% CI 0.30-0.59; P<0.0001). The trials are not directly comparable.

  65. 2021 · Treatment · Melanoma

    Lifileucel: from phase 2 to FDA accelerated approval (2024)

    Lifileucel is made from a person's own immune cells taken from their tumour, grown in a laboratory and given back by infusion. In a single-arm study of people whose melanoma had progressed after earlier treatment, just over a third responded. The US regulator granted accelerated approval in 2024; the European application was withdrawn in 2025.

    Single-arm phase 2 (n=66, all with prior anti-PD-1/PD-L1): investigator-assessed ORR 36% (95% CI 25 to 49), 2 complete and 22 partial responses; median DOR not reached at 18.7 months' follow-up. FDA accelerated approval 16 Feb 2024 on ORR and DOR (ORR 31.5% in 73 patients at the recommended dose). EMA application withdrawn 22 Jul 2025.

  66. 2021 · Treatment · Melanoma

    Tebentafusp: survival benefit in metastatic uveal melanoma (2021)

    Uveal melanoma starts in the eye and behaves differently from skin melanoma. Tebentafusp is an engineered protein that directs the body's T cells to melanoma cells. In a randomised trial of people with a particular tissue type, 73 in 100 were alive at one year, against 59 in 100 given other drugs.

    Open-label phase 3: 378 previously untreated HLA-A*02:01-positive patients randomised 2:1 to tebentafusp (252) or investigator's choice (126; pembrolizumab, ipilimumab or dacarbazine). OS at 1 year 73% vs 59% (HR 0.51, 95% CI 0.37 to 0.71; P<0.001, ITT). 3-year update: median OS 21.6 vs 16.9 months (HR 0.68, 0.54 to 0.87); 27% vs 18% alive at 3 years.

  67. 2021 · Treatment · Multiple myeloma

    BCMA CAR T cells: ide-cel and cilta-cel, from KarMMa to CARTITUDE-4

    CAR T-cell therapy takes a person's own T cells, equips them to recognise BCMA on myeloma cells, and returns them as a single infusion. Single-arm studies reported responses in most heavily treated people. Later randomised trials, at earlier relapse, found longer time without progression than standard regimens, and one has reported longer survival.

    Single-arm: KarMMa (n=128 treated) ORR 73%; CARTITUDE-1 (n=97) ORR 97%. Randomised phase 3, PFS primary: KarMMa-3, ide-cel versus standard regimens (n=386), median 13.3 versus 4.4 months, HR 0.49 (95% CI 0.38 to 0.65); CARTITUDE-4, cilta-cel versus PVd or DPd (n=419), HR 0.26 (0.18 to 0.38). CARTITUDE-4 update at 33.6 months: PFS HR 0.29 (0.22 to 0.39); OS HR 0.55 (0.39 to 0.79).

  68. 2021 · Treatment · Oesophageal cancer

    First-line PD-1 therapy: KEYNOTE-590 and CheckMate 648

    Two large trials added an immune checkpoint inhibitor to chemotherapy as the first treatment for advanced oesophageal cancer. In both, median survival was longer with pembrolizumab or nivolumab added than with chemotherapy alone, and the survival difference was larger in the subgroups with higher PD-L1 expression. FDA approvals followed in 2021 and 2022.

    KEYNOTE-590 (N=749; squamous-cell carcinoma and adenocarcinoma): pembrolizumab plus fluorouracil and cisplatin vs placebo plus chemotherapy; median OS in squamous-cell carcinoma 12.6 vs 9.8 months (HR 0.72; 95% CI 0.60 to 0.88), and 13.9 vs 8.8 months in squamous-cell carcinoma with CPS 10 or more. CheckMate 648 (N=970; squamous only): median OS 15.4 vs 9.1 months with tumour-cell PD-L1 1% or more (nivolumab plus chemotherapy vs chemotherapy; HR 0.54; 99.5% CI 0.37 to 0.80); nivolumab plus ipilimumab also improved OS.

  69. 2021 · Treatment · Oesophageal cancer

    CheckMate 577: adjuvant nivolumab after chemoradiotherapy and surgery

    Some people with oesophageal or junction cancer still have cancer cells in the removed tissue after chemoradiotherapy and surgery. In this trial they received nivolumab or a placebo for up to a year. The median time without return of cancer or death was about 22 months with nivolumab and 11 months with placebo. FDA approved the use in 2021.

    CheckMate 577: randomised 2:1, double-blind, placebo-controlled phase 3; resected stage II or III oesophageal or GEJ cancer with residual pathological disease after neoadjuvant chemoradiotherapy; nivolumab for up to 1 year (N=794). Median DFS 22.4 vs 11.0 months (HR 0.69; 96.4% CI 0.56 to 0.86; P<0.001); median follow-up 24.4 months. Grade 3 or 4 treatment-related adverse events 13% vs 6%.

  70. 2021 · Reversal · Ovarian cancer

    First-line PD-L1 blockade: IMagyn050 and JAVELIN Ovarian 100

    Two large randomised trials added a PD-L1 antibody, atezolizumab or avelumab, to first-line treatment of newly diagnosed ovarian cancer. Neither showed a significant gain in progression-free survival in all participants, and the authors of both reports concluded that the results did not support these drugs in this setting.

    IMagyn050 (N=1301; carboplatin-paclitaxel-bevacizumab plus atezolizumab or placebo): median PFS 19.5 vs 18.4 months, ITT HR 0.92 (95% CI 0.79-1.07); PD-L1-positive 20.8 vs 18.5 months, HR 0.80 (0.65-0.99), not significant at the prespecified level. JAVELIN Ovarian 100 (N=998; stopped for futility at interim analysis): PFS HR 1.43 (1.05-1.95) for avelumab maintenance and 1.14 (0.83-1.56) for avelumab combination vs chemotherapy alone.

  71. 2021 · Treatment · Prostate cancer

    177Lu-PSMA-617 for PSMA-positive mCRPC (VISION, TheraP)

    A radioactive drug that attaches to PSMA, a protein highly expressed in metastatic castration-resistant prostate cancer, was tested after standard drugs stopped working. In VISION, adding it to standard care delayed progression (about 9 versus 3 months) and extended survival (about 15 versus 11 months). In TheraP, survival did not differ from cabazitaxel, with fewer severe side effects.

    VISION (phase 3, N=831; PSMA-PET-positive mCRPC after an ARPI and one or two taxanes): 177Lu-PSMA-617 plus standard care vs standard care alone. Imaging-based PFS 8.7 vs 3.4 months (HR 0.40; 99.2% CI 0.29-0.57); OS 15.3 vs 11.3 months (HR 0.62; 95% CI 0.52-0.74). TheraP (phase 2, N=200, vs cabazitaxel): PSA response 66% vs 37%; OS RMST 19.1 vs 19.6 months (P=0.77).

  72. 2021 · Understanding · Testicular germ cell tumors

    IGCCCG Update: modern survival estimates and refined prognosis

    Two 2021 papers re-examined the IGCCCG groups in men treated from 1990 to 2013: 9,728 with non-seminoma and 2,451 with seminoma. Five-year survival was about 96, 89 and 67 in 100 for good, intermediate and poor non-seminoma, and 95 and 88 in 100 for good and intermediate seminoma.

    Pooled trial and registry data, cisplatin- and etoposide-based first-line chemotherapy, 1990-2013. NSGCT (n=9,728): 5-year OS 96% good, 89% intermediate, 67% poor; PFS 90%, 78%, 54%. Seminoma (n=2,451): 5-year OS 95% good, 88% intermediate; PFS 89%, 79%. New factors: NSGCT LDH cut-off 2.5 x ULN, age, lung metastases; seminoma LDH above 2.5 x ULN (good prognosis 3-year PFS 80% vs 92%).

  73. 2021 · Understanding · Testicular germ cell tumors

    Non-testicular-cancer mortality in long-term survivors (cisplatin era)

    A 2021 Norwegian registry study followed men diagnosed with testicular cancer from 1980 to 2009 and found more deaths from other causes than expected after platinum-based chemotherapy or radiotherapy, led by second cancers. Beyond ten years, death risk exceeded that after surgery at four or more cycles. A smaller cohort linked lifestyle and psychosocial problems with higher mortality.

    Hellesnes 2021: 5,707 Norwegian men diagnosed 1980 to 2009, median follow-up 18.7 years; 665 (12%) died of causes other than testicular cancer. SMR for non-testicular-cancer death 1.23 (95% CI 1.14 to 1.33) overall; 1.23 after platinum-based chemotherapy, 1.28 after radiotherapy; second cancers 1.53. Versus surgery beyond 10 years, more than four cycles: HR 2.04 (95% CI 1.25 to 3.35). Fosså 2022 (775 men): cumulative 20-year mortality 14%.

  74. 2021 · Treatment · Thyroid cancer

    COSMIC-311: cabozantinib after prior VEGFR therapy in DTC

    Some people with radioiodine-refractory thyroid cancer have already been treated with lenvatinib or sorafenib when the cancer grows again. In a placebo-controlled trial of such patients, cabozantinib delayed progression: the median had not been reached with cabozantinib, against about two months with placebo. The FDA extended cabozantinib's approval to this group in September 2021.

    COSMIC-311 (n=187; 2:1 cabozantinib 60 mg daily vs placebo; prior lenvatinib or sorafenib). Interim PFS (ITT): median not reached vs 1.9 months (HR 0.22; 96% CI 0.13 to 0.36; p<0.0001). ORR in the first 100 randomised (OITT) 15% vs 0% (p=0.028), which did not meet the prespecified alpha of 0.01. Exploratory extended cut (n=258): median PFS 11.0 vs 1.9 months (HR 0.22; 96% CI 0.15 to 0.32).

  75. 2022 · Treatment · Bladder cancer

    N-803 plus BCG in BCG-unresponsive NMIBC

    Nogapendekin alfa inbakicept (N-803) is an interleukin-15 activator given into the bladder together with BCG. In a single-group study of people whose carcinoma in situ no longer responded to BCG, about seven in ten had a complete response. The US regulator approved it in April 2024.

    QUILT-3.032 cohort A (82 patients, BCG-unresponsive CIS with or without papillary disease): NAI plus BCG, complete response 71% (58/82; 95% CI 59.6 to 80.3), median duration 26.6 months; at 24 months in responders, cystectomy avoidance 89.2%, bladder cancer-specific survival 100%. Cohort B (72 papillary): 12-month DFS 55.4% (95% CI 42.0 to 66.8). FDA approval 22 April 2024.

  76. 2022 · Treatment · Breast cancer

    T-DXd in HER2-low breast cancer (DESTINY-Breast04, -06)

    In 2022 a trial of trastuzumab deruxtecan, an antibody linked to a chemotherapy drug, in metastatic breast cancers with low HER2 levels reported delayed progression and longer survival than the doctor's choice of chemotherapy. The report states earlier HER2-directed drugs had been ineffective in this group. Lung inflammation was a recognised risk.

    DESTINY-Breast04: phase 3, 2:1 randomisation of 557 patients with HER2-low (IHC 1+ or 2+/ISH-) metastatic disease after 1-2 chemotherapy lines, trastuzumab deruxtecan vs physician's choice. Hormone receptor-positive cohort (494): median PFS 10.1 vs 5.4 months (HR 0.51); OS 23.9 vs 17.5 months (HR 0.64; P=0.003). Long-term update: overall-cohort OS 22.9 vs 16.8 months (HR 0.69; 95% CI 0.55 to 0.86). Adjudicated drug-related ILD: 12.1%.

  77. 2022 · Treatment · Breast cancer

    DESTINY-Breast03: T-DXd versus T-DM1 in HER2-positive disease

    In people with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, trastuzumab deruxtecan was compared directly with trastuzumab emtansine. The newer drug delayed progression for longer. Lung inflammation was a recognised risk.

    Phase 3 (524 patients previously treated with trastuzumab and a taxane): trastuzumab deruxtecan vs trastuzumab emtansine. Primary analysis: 12-month PFS (blinded central review) 75.8% vs 34.1% (HR 0.28; 95% CI 0.22 to 0.37; P<0.001); adjudicated drug-related ILD 10.5% vs 1.9%. Updated analysis: median PFS 28.8 vs 6.8 months (HR 0.33); OS HR 0.64 (95% CI 0.47 to 0.87), median not reached.

  78. 2022 · Treatment · Breast cancer

    Elacestrant: the first oral SERD (EMERALD)

    Elacestrant is an oral drug that breaks down the oestrogen receptor. In the EMERALD trial it delayed progression compared with standard hormone therapy in women whose cancer had progressed after earlier treatment that included a CDK4/6 inhibitor, and the benefit was clearest when the tumour carried an ESR1 mutation. Regulators approved it for that group.

    EMERALD (N=477; ER-positive, HER2-negative, pretreated including a CDK4/6 inhibitor): PFS by blinded central review HR 0.70 (0.55-0.88) overall and 0.55 (0.39-0.77) in ESR1-mutated disease; ESR1-mutated median PFS 3.8 vs 1.9 months (FDA page and paper Discussion). 12-month PFS in ESR1-mutated disease 26.8% vs 8.2%. Interim overall survival HR 0.75 (0.54-1.04) overall, not significant.

  79. 2022 · Treatment · Cervical cancer

    EMPOWER-Cervical 1: cemiplimab versus chemotherapy after platinum

    In 608 people whose cervical cancer had progressed after first-line platinum chemotherapy, the immune checkpoint drug cemiplimab was compared with chemotherapy chosen by the treating doctor. In the whole trial population, which was enrolled regardless of PD-L1 result, median survival was 12.0 months with cemiplimab and 8.5 months with chemotherapy.

    Phase 3, open-label, randomised 1:1 (N=608): cemiplimab 350 mg every 3 weeks vs investigator's choice single-agent chemotherapy after progression on first-line platinum-containing chemotherapy, regardless of PD-L1 status. Median OS 12.0 vs 8.5 months (HR 0.69; 95% CI 0.56-0.84; P<0.001); PFS HR 0.75 (95% CI 0.63-0.89); ORR 16.4% vs 6.3%. Grade 3 or higher adverse events 45.0% vs 53.4%.

  80. 2022 · Treatment · Chronic lymphocytic leukaemia

    Fixed-duration combinations: GLOW and CLL13 (GAIA)

    Two trials tested fixed-length venetoclax combinations as first treatment. GLOW, in older or less fit people, found ibrutinib plus venetoclax kept people free of progression longer than chlorambucil plus obinutuzumab. CLL13, in fit people, found venetoclax with obinutuzumab (with or without ibrutinib) did better than chemoimmunotherapy; venetoclax with rituximab was not significantly better.

    GLOW (211 randomised; age 65 or older, or coexisting conditions): ibrutinib-venetoclax vs chlorambucil-obinutuzumab, IRC-assessed PFS HR 0.216 (95% CI 0.131 to 0.357; P<0.001) at median 27.7 months. CLL13 (926 fit patients without TP53 aberrations): undetectable MRD at month 15 86.5% (venetoclax-obinutuzumab) and 92.2% (plus ibrutinib) vs 52.0% with chemoimmunotherapy; 3-year PFS 87.7% and 90.5% vs 75.5%; venetoclax-rituximab 57.0% and 80.8%, not significantly better.

  81. 2022 · Treatment · Chronic lymphocytic leukaemia

    Zanubrutinib: SEQUOIA and the ALPINE head-to-head with ibrutinib

    Zanubrutinib is an oral BTK inhibitor tested against bendamustine-rituximab in untreated CLL and against ibrutinib in relapsed disease. Progression-free survival was longer with zanubrutinib in both trials. In the head-to-head trial more people responded, and fewer had atrial fibrillation. The US regulator approved it for CLL in 2023.

    SEQUOIA (n=590; 241 vs 238 randomised, no del(17p)): PFS by independent review HR 0.42 (95% CI 0.28 to 0.63) vs bendamustine-rituximab at median follow-up 26.2 months. ALPINE (n=652, vs ibrutinib): ORR (primary, first 415 patients) 78.3% vs 62.5% (P<.001); final investigator-assessed PFS HR 0.65 (0.49 to 0.86), 24-month PFS 78.4% vs 65.9%.

  82. 2022 · Treatment · Colorectal cancer

    DYNAMIC: ctDNA-guided adjuvant therapy in stage II colon cancer

    In DYNAMIC, people with stage II colon cancer were randomly assigned to have chemotherapy decisions guided by a blood test for circulating tumour DNA or by standard features of the tumour. Fewer people in the test-guided group had chemotherapy, about fifteen in a hundred against twenty-eight, and two-year recurrence-free survival was about the same, near ninety-three percent.

    DYNAMIC (Tie 2022): 455 patients with stage II colon cancer randomised 2:1 to ctDNA-guided (n=302) or standard management (n=153). Adjuvant chemotherapy 15% vs 28%. 2-year RFS 93.5% vs 92.4% (difference 1.1 points, 95% CI -4.1 to 6.2; noninferiority margin -8.5), median follow-up 37 months. 5-year RFS 88% vs 87%; 5-year OS 93.8% vs 93.3% (HR 1.05, P=0.887). DYNAMIC-III (stage III): de-escalation did not meet its noninferiority margin.

  83. 2022 · Treatment · Colorectal cancer

    KRAS G12C inhibitors with anti-EGFR antibodies

    A small share of bowel cancers carry a KRAS G12C change. Used alone, drugs aimed at it worked modestly. Paired with an anti-EGFR antibody, one drug shrank tumours in nearly half of 28 evaluable people in a non-randomised study; its US approval was withdrawn in 2026. Another delayed progression against standard treatment in a randomised trial.

    KRYSTAL-1 (phase 1-2, nonrandomised, KRAS G12C colorectal cancer): adagrasib + cetuximab, ORR 46% (95% CI 28-66; 28 evaluable patients), median PFS 6.9 months (32 patients). CodeBreaK 300 (phase 3, n=160): sotorasib 960 mg + panitumumab vs investigator's choice, median PFS 5.6 vs 2.2 months (HR 0.49, 95% CI 0.30-0.80; P=0.006); ORR 26.4% vs 0%. OS HR 0.70 (95% CI 0.41-1.18; P=0.20).

  84. 2022 · Detection · Colorectal cancer

    NordICC: invitation to screening colonoscopy

    In a trial in four European countries (follow-up data from three), people aged 55 to 64 were randomly invited to one screening colonoscopy or not invited. Fewer than half of those invited had the examination. After about ten years, fewer colorectal cancers were found in the invited group; deaths from colorectal cancer were not clearly different, with an imprecise estimate.

    Pragmatic randomised trial of invitation to one screening colonoscopy vs usual care (ages 55-64; 84,585 with follow-up in Poland, Norway, Sweden); 42.0% of the invited group were screened. Intention-to-screen at 10 years: colorectal cancer risk 0.98% vs 1.20% (risk ratio 0.82, 95% CI 0.70-0.93); colorectal cancer death 0.28% vs 0.31% (risk ratio 0.90, 0.64-1.16); all-cause death risk ratio 0.99 (0.96-1.04). Separate instrumental-variable per-protocol analysis: incidence reduction 35 to 41%; mortality intervals include 1.

  85. 2022 · Treatment · Colorectal cancer

    Dostarlimab alone for mismatch repair-deficient rectal cancer

    In a small phase 2 study, people with rectal cancer caused by faulty DNA mismatch repair received the immunotherapy drug dostarlimab for six months. In the first twelve to complete treatment and be followed for at least six months, no tumour could be detected afterwards, and none had had radiation or surgery. Follow-up was short.

    Phase 2, single-arm rectal cohort (NCT04165772), stage II or III dMMR rectal adenocarcinoma, dostarlimab every 3 weeks for 6 months, then chemoradiotherapy and surgery unless clinical complete response. 12 of 12 patients with at least 6 months of follow-up (range 6-25 months) had a clinical complete response (100%; 95% CI 74-100); no grade 3 or higher adverse events. 2025 update: all 49 patients who completed treatment had a clinical complete response; 37 sustained it at 12 months.

  86. 2022 · De-escalation · Colorectal cancer

    OPRA: total neoadjuvant therapy and selective watch-and-wait

    In OPRA, 324 people with stage II or III rectal cancer had chemotherapy and chemoradiotherapy in one of two orders; those whose tumour disappeared or nearly did could watch and wait. After about five years, roughly seven in ten were free of disease in both groups. Survival without total mesorectal excision (organ preservation) was higher when chemotherapy came last.

    Randomised phase 2, 324 patients with stage II/III rectal adenocarcinoma: induction chemotherapy then chemoradiotherapy (INCT-CRT) vs chemoradiotherapy then consolidation chemotherapy (CRT-CNCT); TME or watch-and-wait by response. Two stand-alone studies against a historical 3-year DFS of 75%, not head to head. 3-year DFS 76% in each; 5-year DFS 71% vs 69% (P=0.68); 5-year TME-free survival 39% vs 54% (P=0.012).

  87. 2022 · Reversal · Gastric and gastro-oesophageal junction cancer

    Later-line pembrolizumab in gastric cancer: approved, then withdrawn

    In 2017 the US regulator gave pembrolizumab an accelerated approval for stomach cancer that had progressed after two or more treatments, based on tumour response. A separate 2018 randomised trial against paclitaxel in second-line treatment did not show significantly longer survival. The indication was withdrawn from the US label in February 2022; the FDA letter gives no reason.

    KEYNOTE-059 (phase 2, single-arm, 259 patients): ORR 11.6% (95% CI 8.0 to 16.1); 15.5% PD-L1-positive, 6.4% PD-L1-negative. KEYNOTE-061 (phase 3, second line, CPS 1 or more, 395 patients): median OS 9.1 vs 8.3 months for pembrolizumab vs paclitaxel, HR 0.82 (95% CI 0.66 to 1.03), one-sided p=0.0421; PFS HR 1.27. FDA accelerated approval 22 Sep 2017; withdrawn 4 Feb 2022.

  88. 2022 · Reversal · Head and neck cancer

    First-line immunotherapy combinations: no overall survival gain

    Four randomised trials tested a second drug alongside immunotherapy as first treatment for head and neck cancer that had returned or spread. The combinations were durvalumab with tremelimumab, nivolumab with ipilimumab, lenvatinib with pembrolizumab, and feladilimab with pembrolizumab. None improved overall survival over its comparator.

    Four randomised first-line R/M SCCHN trials, not pooled. KESTREL (PD-L1-high): durvalumab vs EXTREME, OS HR 0.96 (95% CI 0.69-1.32); durvalumab plus tremelimumab vs EXTREME, HR 1.05 (0.80-1.39). CheckMate 651: nivolumab plus ipilimumab vs EXTREME, OS HR 0.95 (97.9% CI 0.80-1.13). LEAP-010: lenvatinib plus pembrolizumab vs placebo plus pembrolizumab, PFS HR 0.64, OS HR 1.15 (95% CI 0.91-1.45). INDUCE-3: OS HR 1.51 (95% CI 0.99-2.29).

  89. 2022 · Treatment · Hepatocellular carcinoma

    HIMALAYA: tremelimumab plus durvalumab (STRIDE) versus sorafenib

    In 1,171 people with liver cancer that could not be removed, three treatments were compared: one priming dose of tremelimumab plus regular durvalumab, durvalumab alone, and sorafenib. Median survival was about 16 months with the combination and about 14 months with sorafenib. About three in ten on the combination were alive at three years, against two in ten on sorafenib.

    HIMALAYA (open-label phase 3, N=1171, no prior systemic therapy): STRIDE (n=393), durvalumab (n=389) or sorafenib (n=389). Median OS 16.43 vs 16.56 vs 13.77 months; STRIDE vs sorafenib HR 0.78 (96.02% CI 0.65-0.93; P=0.0035); durvalumab non-inferior (HR 0.86; margin 1.08). Median PFS not significantly different. Updates: 4-year OS HR 0.78 (95% CI 0.67-0.92); 60-month OS 19.6% vs 9.4% (HR 0.76; 95% CI 0.65-0.89).

  90. 2022 · Treatment · Hodgkin lymphoma

    AHOD1331: brentuximab vedotin in pediatric high-risk HL

    In children, adolescents and young adults aged 2 to 21 with high-risk Hodgkin lymphoma, swapping bleomycin for brentuximab vedotin in standard chemotherapy raised the share free of relapse, progression, a second cancer or death at three years from about 83 in 100 to about 92 in 100, with similar toxic effects reported.

    Open-label phase 3 (600 enrolled, 587 eligible), ages 2 to 21 years, stage IIB with bulk or stage IIIB, IVA or IVB. Brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide versus a bleomycin-containing standard regimen, five cycles. 3-year EFS 92.1% versus 82.5% (HR 0.41, 95% CI 0.25 to 0.67; P<0.001); median follow-up 42.1 months. 3-year OS 99.3% versus 98.5%.

  91. 2022 · Reversal · Kidney cancer (renal cell carcinoma)

    Adjuvant checkpoint trials: IMmotion010, CheckMate 914, PROSPER

    Three trials tested immunotherapy around kidney cancer surgery: atezolizumab, nivolumab with ipilimumab, and perioperative nivolumab. None lengthened the time free of recurrence compared with placebo or surgery alone, and the nivolumab trial stopped early for futility. Side effects were more frequent with immunotherapy.

    Three phase 3 trials, none showing a primary-endpoint benefit. IMmotion010 (atezolizumab vs placebo, n=778): investigator-assessed DFS HR 0.93 (95% CI 0.75-1.15; P=0.50). CheckMate 914 part A (nivolumab plus ipilimumab vs placebo, n=816): central-review DFS HR 0.92 (95% CI 0.71-1.19; P=0.53). PROSPER EA8143 (perioperative nivolumab vs surgery only, n=819, open-label): RFS HR 0.94 (95% CI 0.74-1.21; one-sided P=0.32); stopped for futility.

  92. 2022 · Treatment · Lung cancer

    CheckMate 816: neoadjuvant nivolumab plus chemotherapy

    Before surgery for lung cancer that could be removed, nivolumab added to platinum chemotherapy was compared with chemotherapy alone. More people had no living cancer left at surgery, and the cancer took longer to return or progress. A later report found longer overall survival. The FDA approved the combination before the trial was published.

    Open-label phase 3; resectable stage IB-IIIA NSCLC; three cycles of neoadjuvant nivolumab plus platinum chemotherapy vs chemotherapy alone, then surgery (179 vs 179 concurrently randomised). Median EFS 31.6 vs 20.8 months (HR 0.63; 97.38% CI 0.43-0.91). pCR 24.0% vs 2.2%. Final OS: HR 0.72 (95% CI 0.523-0.998); 5-year OS 65.4% vs 55.0%.

  93. 2022 · De-escalation · Lung cancer

    Segmentectomy and sublobar resection vs lobectomy (2022-2023)

    Two randomised trials in small peripheral lung cancers (2 cm or less) compared removing less lung with removing a whole lobe. In a Japanese trial, about 94 in 100 patients were alive at five years after segmentectomy and 91 in 100 after lobectomy. In a second trial, about 64 in 100 were alive and disease-free at five years either way.

    JCOG0802/WJOG4607L (phase 3, n=1106, clinical stage IA, 2 cm or less, consolidation-to-tumour ratio above 0.5): 5-year OS 94.3% segmentectomy vs 91.1% lobectomy (HR 0.663, 95% CI 0.474-0.927), median follow-up 7.3 years; 5-year RFS 88.0% vs 87.9%; local relapse 10.5% vs 5.4%. CALGB 140503 (phase 3, n=697, T1aN0, node-negative): primary DFS HR 1.01 (90% CI 0.83-1.24); 5-year DFS 63.6% vs 64.1%. Endpoints differ.

  94. 2022 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    Glofitamab and epcoritamab in relapsed DLBCL (2022-2023)

    Two antibodies that link T cells to CD20-carrying lymphoma cells, glofitamab and epcoritamab, produced complete responses in about 4 in 10 heavily pretreated people with large B-cell lymphoma in single-arm studies. The FDA granted both accelerated approval in 2023.

    Single-arm phase 2 reports in relapsed or refractory large B-cell lymphoma after at least two lines. Glofitamab (fixed-duration, 155 enrolled): IRC complete response 39% (95% CI 32 to 48), median follow-up 12.6 months; 12-month PFS 37%. Epcoritamab (subcutaneous, 157 treated): ORR 63.1% (55.0 to 70.6), CR 38.9%; at 25.1 months CR 40.1%, 24-month PFS 27.8%. FDA accelerated approvals 19 May and 15 June 2023.

  95. 2022 · Treatment · Non-Hodgkin lymphoma (DLBCL and follicular)

    Mosunetuzumab and epcoritamab in relapsed follicular lymphoma

    Antibodies that link a person's T cells to lymphoma cells produced responses in most people with relapsed follicular lymphoma in single-arm studies: complete response in about six in ten with mosunetuzumab, response in about eight in ten with epcoritamab. Both received FDA accelerated approval. A randomised trial then tested adding epcoritamab to lenalidomide and rituximab.

    Single-arm phase 2 studies, relapsed or refractory FL after two or more lines. Mosunetuzumab (n=90): IRC-assessed CR rate 60.0% (95% CI 49.1 to 70.2). Epcoritamab (pivotal cohort n=128): ORR 82.0%, CR rate 62.5%. Randomised phase 3 EPCORE FL-1 (n=488, interim analysis, median follow-up 14.8 months): ORR 95% versus 79%; 16-month PFS 85.5% versus 40.2% (HR 0.21, 95% CI 0.14 to 0.31).

  96. 2022 · Treatment · Melanoma

    TIL therapy versus ipilimumab: randomised phase 3 trial (2022)

    A randomised trial led by the Netherlands Cancer Institute compared infusion of a patient's own tumour-infiltrating immune cells with the antibody ipilimumab in advanced melanoma, mostly refractory to earlier PD-1 treatment. Time without progression was longer with the cell therapy, but everyone who received it had a severe treatment-related side effect, mainly from the preparatory chemotherapy.

    Phase 3, open-label, 168 patients with unresectable stage IIIC or IV melanoma (86% anti-PD-1 refractory), TIL vs ipilimumab 3 mg/kg, 1:1. Median PFS 7.2 vs 3.1 months (HR 0.50, 95% CI 0.35 to 0.72; P<0.001, ITT); ORR 49% vs 21%. Median OS 25.8 vs 18.9 months. Grade 3 or higher treatment-related events: all TIL recipients, 57% with ipilimumab.

  97. 2022 · Treatment · Melanoma

    Relatlimab plus nivolumab: RELATIVITY-047 and LAG-3 blockade (2022)

    In untreated advanced melanoma, adding relatlimab, an antibody against the immune checkpoint LAG-3, to nivolumab delayed progression compared with nivolumab alone. Survival differences at three and four years were reported as descriptive. The FDA approved the combination in March 2022; in Europe it is limited to tumours with low PD-L1.

    RELATIVITY-047 (phase 2/3, n=714, untreated): relatlimab plus nivolumab vs nivolumab, median PFS 10.1 vs 4.6 months (HR 0.75; 95% CI 0.62 to 0.92; P=0.006); 12-month PFS 47.7% vs 36.0%. Grade 3 or 4 treatment-related adverse events 18.9% vs 9.7%. At 3 years median OS 51.0 vs 34.1 months (HR 0.80; 95% CI 0.66 to 0.99), descriptive. EMA indication restricted to tumour PD-L1 below 1%.

  98. 2022 · Treatment · Melanoma

    Sequencing in BRAF-mutant disease: DREAMseq, SECOMBIT and EBIN

    For melanoma with a BRAF mutation, two sets of drugs are available, and trials asked which to give first. In DREAMseq, starting with nivolumab plus ipilimumab was associated with better two-year survival than starting with dabrafenib plus trametinib. SECOMBIT did not compare arms. In EBIN, a targeted lead-in before immunotherapy did not improve progression-free survival.

    DREAMseq (phase 3, n=265, stopped early): 2-year OS 71.8% (nivolumab plus ipilimumab first) vs 51.5% (dabrafenib plus trametinib first), P=0.010. SECOMBIT (noncomparative phase 2, n=209): 3-year OS 54%, 62% and 60% across the three sequences. EBIN (phase 2, n=271): encorafenib plus binimetinib induction did not improve PFS (median 9 vs 9 months; P=0.36).

  99. 2022 · Treatment · Multiple myeloma

    Bispecifics: teclistamab, talquetamab, elranatamab, linvoseltamab

    Bispecific antibodies hold a T cell and a myeloma cell together so the T cell can attack. Teclistamab, elranatamab and linvoseltamab target BCMA; talquetamab targets GPRC5D. In single-arm studies of heavily treated people, about half to nearly three-quarters responded. The US approved all four between 2022 and 2025.

    Single-arm studies. MajesTEC-1 (teclistamab, n=165; ORR primary): ORR 63.0%, median PFS 11.3 months. MagnetisMM-3 cohort A (elranatamab, n=123; ORR primary): 61.0%. LINKER-MM1 (linvoseltamab, phase I/II): 71% at 200 mg, 48% at 50 mg. MonumenTAL-1 (talquetamab) is the phase 1 report: 70% and 64% at two subcutaneous doses. Cytokine release syndrome: 72.1% with teclistamab, 57.7% with elranatamab. FDA accelerated approvals 2022 to 2025; teclistamab converted in 2026.

  100. 2022 · Treatment · Ovarian cancer

    Mirvetuximab soravtansine for folate receptor-high disease

    Mirvetuximab soravtansine is an antibody joined to a chemotherapy drug that targets folate receptor alpha on some ovarian cancer cells. In a single-arm study, about one in three people with platinum-resistant disease responded. In a randomised trial, those given it lived about four months longer than those given chemotherapy, and their disease progressed later.

    SORAYA (single-arm phase 2, FRα-high, N=106): confirmed ORR 32.4% (95% CI 23.6-42.2), median DOR 6.9 months. MIRASOL (phase 3, FRα-high, N=453, vs investigator's-choice chemotherapy): median PFS 5.62 vs 3.98 months (p<0.001); ORR 42.3% vs 15.9%; median OS 16.46 vs 12.75 months, HR 0.67 (0.50-0.89), p=0.005.

  101. 2022 · Reversal · Ovarian cancer

    PARP inhibitor later-line ovarian indications withdrawn (2022)

    In 2022 three PARP inhibitors lost their later-line ovarian cancer treatment indications in the US: rucaparib in June and olaparib in August by voluntary withdrawal, niraparib in September by removal. In December, recurrent maintenance with niraparib and rucaparib was limited to BRCA-mutated disease (germline for niraparib). The FDA letters give no reasons.

    FDA letters: rucaparib (two or more prior lines) withdrawn 10 June 2022; olaparib (three or more) 26 August; niraparib (three or more, HRD-positive) removed 14 September; recurrent maintenance restricted to BRCA-mutated disease for niraparib (8 December) and rucaparib (21 December). ARIEL4 (N=349), reported separately: PFS HR 0.67 (95% CI 0.52-0.86); final OS 19.4 vs 25.4 months, rucaparib vs chemotherapy, HR 1.3 (1.0-1.7), 69% crossover.

  102. 2022 · Treatment · Ovarian cancer

    Low-grade serous disease: MEK inhibition (GOG 281, RAMP 201)

    Low-grade serous ovarian cancer grows slowly and often responds poorly to chemotherapy. In GOG 281, the MEK inhibitor trametinib delayed progression by about six months compared with standard treatment. In RAMP 201, about three in ten responded to avutometinib with defactinib. The FDA granted accelerated approval for KRAS-mutated disease in 2025.

    GOG 281 (phase 2/3, N=260, recurrent LGSOC): trametinib vs standard of care, median PFS 13.0 vs 7.2 months, HR 0.48 (95% CI 0.36-0.64); ORR 26% vs 6%. RAMP 201 (phase 2, 115 treated): avutometinib plus defactinib ORR 31%, 44% in KRAS-mutant and 17% in KRAS wild-type; median DOR 31.1 months. MILO (binimetinib) did not improve PFS: HR 1.21 (0.79-1.86).

  103. 2022 · Treatment · Pancreatic cancer

    KRAS G12C inhibitors in the small G12C-mutated subset

    About one to two in every hundred pancreatic cancers carry a KRAS G12C change. In small single-group studies, 8 of 38 treated people responded to sotorasib, and 7 of 21 pancreatic patients to adagrasib. The US labels in the openFDA database in October 2026 list no pancreatic cancer indication for either drug.

    Single-group studies, previously treated KRAS G12C-mutated pancreatic cancer. Sotorasib (CodeBreaK 100, phase 1-2, pooled n=38): centrally confirmed ORR 21% (95% CI 10-37), median PFS 4.0 months (2.8-5.6), median OS 6.9 months (5.0-9.1). Adagrasib (KRYSTAL-1, mixed-tumour cohort): ORR 7/21 (33.3%) in pancreatic cancer. G12C occurs in about 1 to 2% of pancreatic cancers.

  104. 2022 · Reversal · Pancreatic cancer

    APACT: adjuvant nab-paclitaxel plus gemcitabine, DFS not met

    APACT compared nab-paclitaxel plus gemcitabine with gemcitabine alone after pancreatic cancer surgery. The main measure, disease-free survival judged by independent reviewers, did not differ: 19.4 against 18.8 months. Median survival was 41.8 against 37.7 months at five years of follow-up, which the authors treat as descriptive because the main measure was not met.

    APACT (Tempero 2023): 866 patients with resected PDAC, nab-paclitaxel plus gemcitabine vs gemcitabine, six cycles. Primary endpoint independently assessed DFS not met: 19.4 vs 18.8 months (HR 0.88, 95% CI 0.729-1.063, P=.18). Investigator-assessed DFS 16.6 vs 13.7 months (HR 0.82, P=.02). OS at 5-year follow-up 41.8 vs 37.7 months (HR 0.80, 95% CI 0.678-0.947). Grade 3 or worse events 86% vs 68%.

  105. 2022 · Treatment · Prostate cancer

    Triplet therapy: ADT, docetaxel and an AR inhibitor (ARASENS, PEACE-1)

    In 2022 two trials added a third drug to hormone therapy plus docetaxel in metastatic hormone-sensitive prostate cancer. In ARASENS, adding darolutamide gave a hazard ratio for death of 0.68 against placebo. In PEACE-1, adding abiraterone gave 0.75 among men who received docetaxel. The FDA approved darolutamide with docetaxel in August 2022.

    ARASENS (n=1306; darolutamide 600 mg twice daily versus placebo, both with ADT and docetaxel): OS HR 0.68 (95% CI 0.57-0.80; P<0.001). PEACE-1 (open-label 2x2 factorial; de novo metastatic castration-sensitive): abiraterone versus none in the ADT-plus-docetaxel population (355 per group), OS HR 0.75 (95.1% CI 0.59-0.95; P=0.017), rPFS HR 0.50 (99.9% CI 0.34-0.71). Grade 3 or worse adverse events in that population: 63% versus 52%.

  106. 2022 · Treatment · Prostate cancer

    PARP inhibitor plus ARPI first line (PROpel, MAGNITUDE, TALAPRO-2)

    Three large trials added a PARP inhibitor to a hormonal drug as first treatment for metastatic castration-resistant prostate cancer. Each delayed progression on imaging; in MAGNITUDE and TALAPRO-2 the effect looked larger with BRCA or other DNA-repair gene changes. Final survival was longer with talazoparib plus enzalutamide (about 46 versus 37 months) but not significantly different in PROpel or MAGNITUDE.

    First-line mCRPC, PARP inhibitor plus ARPI vs placebo plus ARPI. PROpel (olaparib + abiraterone, all-comers): imaging-based PFS 24.8 vs 16.6 months (HR 0.66); final OS 42.1 vs 34.7 months (HR 0.81; 95% CI 0.67-1.00; P=0.054). MAGNITUDE (niraparib + abiraterone, HRR+): rPFS HR 0.73; final OS HR 0.931 (0.720-1.203). TALAPRO-2 (talazoparib + enzalutamide): rPFS HR 0.63; final OS 45.8 vs 37.0 months (HR 0.80; 0.66-0.96).

  107. 2022 · De-escalation · Testicular germ cell tumors

    TRISST: fewer scans and MRI instead of CT in seminoma surveillance

    Men under surveillance for stage I seminoma have regular scans. The TRISST trial randomised them to three or seven scans, and to CT or MRI. Advanced relapse was rare in every group. MRI and the shorter schedule were statistically non-inferior, although the shorter schedule had slightly more advanced relapses.

    TRISST (phase III non-inferiority, 2x2 factorial; 669 patients, 35 UK centres, median follow-up 72 months): 6-year incidence of stage IIC or higher relapse 2.8% with three scans vs 0.3% with seven (absolute increase 2.5%, 90% CI 1.0-4.1; non-inferior), and 0.6% with MRI vs 2.6% with CT (1.9% decrease; non-inferior). Ten such events overall; 82 patients (12%) relapsed; 5-year survival 99%, no tumour-related deaths.

  108. 2022 · De-escalation · Testicular germ cell tumors

    Primary RPLND for stage IIA/B seminoma: PRIMETEST

    Stage IIA or IIB seminoma is usually treated with radiotherapy or chemotherapy. In this small single-arm trial, 33 men had lymph node surgery alone. About one in three had a recurrence, which missed the trial's target, so the authors did not recommend surgery alone outside trials.

    PRIMETEST (single-arm, single-centre phase 2; 33 patients, 2016-2021) of primary RPLND alone for seminoma, clinical stage IIA/B. After median follow-up 32 months, ten recurrences (30%, 95% CI 16-49%); primary endpoint (progression-free survival at 36 months, positive if fewer than 30% recurred) not met. Three of ten were infield recurrences; 3 of 33 (9%) had pN0 disease. Authors: surgery alone not recommended outside a trial.

  109. 2022 · De-escalation · Thyroid cancer

    ESTIMABL2 and IoN: low-risk thyroid cancer without radioiodine

    Two randomised trials asked whether people with low-risk thyroid cancer need radioactive iodine after the thyroid is removed. In both, follow-up without radioiodine was judged non-inferior on the trial's main measure: ESTIMABL2 in France at three years and IoN in the UK at five years. Both were in disease the authors call low-risk.

    ESTIMABL2 (phase 3; n=776), no radioiodine vs 1.1 GBq ablation after rhTSH: composite event-free rate at 3 years 95.6% vs 95.9% (difference -0.3 points; 90% CI -2.7 to 2.2), non-inferiority met; at 5 years 93.2% vs 94.8%. IoN (UK; n=504): 5-year recurrence-free rate 97.9% (no ablation) vs 96.3% (ablation) in the ITT analysis; absolute risk difference 0.5 points as published (95% CI -2.2 to 3.2; p=0.033 for non-inferiority). Primary endpoints differ.

  110. 2023 · Treatment · Acute myeloid leukaemia (including APL)

    QuANTUM-First: quizartinib with chemotherapy in FLT3-ITD AML

    In 2023 the US approved quizartinib, added to chemotherapy and then continued alone, for adults with newly diagnosed AML carrying a FLT3-ITD mutation. In the QuANTUM-First trial, median survival was about 32 months with quizartinib and about 15 months with placebo.

    QuANTUM-First: randomised, double-blind, placebo-controlled phase 3 in FLT3-ITD-positive newly diagnosed AML aged 18-75 (n=539; 268 quizartinib, 271 placebo), with 7 + 3 induction, consolidation and up to 3 years' continuation. Median OS 31.9 months (95% CI 21.0-not estimable) vs 15.1 months (13.2-26.2); HR 0.78 (95% CI 0.62-0.98; p=0.032); median follow-up 39.2 months.

  111. 2023 · Treatment · Acute myeloid leukaemia (including APL)

    Menin inhibitors: revumenib and ziftomenib in KMT2A or NPM1 leukemia

    Menin inhibitors are oral drugs for leukemias with KMT2A changes or NPM1 mutations. In single-arm studies of heavily pretreated people, about one in four reached a complete remission, sometimes with partial blood-count recovery. The US approved revumenib in 2024 and 2025 and ziftomenib in 2025 for relapsed or refractory disease.

    Single-arm studies, no comparator. Revumenib (AUGMENT-101 phase 2): KMT2A-rearranged acute leukemia, CR+CRh 22.8% (95% CI 12.7-35.8; n=57 evaluable) and NPM1-mutated AML, 23.4% (n=64), each tested against a 10% null (P=.0036; 1-sided P=.0014). Ziftomenib (KOMET-001 phase 2, NPM1-mutated, n=92): CR/CRh 22% (95% CI 14-32; P=.0058 against a 12% historical benchmark), median OS 6.6 months (95% CI 3.6-8.6).

  112. 2023 · Treatment · Bladder cancer

    EV-302: enfortumab vedotin plus pembrolizumab as first-line

    In 886 people with untreated advanced bladder (urothelial) cancer, enfortumab vedotin plus pembrolizumab was linked to median survival of about 31.5 months, compared with about 16 months for platinum-based chemotherapy. Side effects differed between the two treatments.

    Open-label phase 3 (N=886): enfortumab vedotin plus pembrolizumab vs gemcitabine plus cisplatin or carboplatin. Median PFS (blinded central review) 12.5 vs 6.3 months (HR 0.45; 95% CI 0.38-0.54); median OS 31.5 vs 16.1 months (HR 0.47; 95% CI 0.38-0.58); both P<0.001. At 2.5 years' median follow-up, OS HR 0.51 (95% CI 0.43-0.61). FDA regular approval 15 December 2023.

  113. 2023 · Reversal · Cervical cancer

    OUTBACK and CALLA: adjuvant chemotherapy and durvalumab add-ons

    Two large trials tested adding treatment to chemoradiation for locally advanced cervical cancer. Adding four cycles of chemotherapy afterwards (OUTBACK) did not improve five-year survival and increased short-term toxicity. Adding the immunotherapy durvalumab (CALLA) did not significantly improve progression-free survival in the first analysis.

    OUTBACK (phase 3, open-label, N=926): adjuvant carboplatin-paclitaxel after cisplatin chemoradiotherapy vs chemoradiotherapy alone; 5-year OS 72% vs 71%, HR 0.90 (95% CI 0.70 to 1.17; p=0.81). CALLA (phase 3, double-blind, N=770): durvalumab or placebo with and after chemoradiotherapy; PFS HR 0.84 (0.65 to 1.08; p=0.17), 12-month PFS 76.0% vs 73.3% at median follow-up of about 18 months.

  114. 2023 · Treatment · Cervical cancer

    BEATcc and COMPASSION-16: atezolizumab, cadonilimab

    Two more phase 3 trials added a checkpoint antibody to first-line chemotherapy for cervical cancer that had spread or returned. Atezolizumab on top of bevacizumab and chemotherapy, and cadonilimab on top of chemotherapy in a Chinese trial, were each linked to longer progression-free and overall survival than the control.

    BEATcc (N=410; atezolizumab added to bevacizumab, platinum and paclitaxel): median PFS 13.7 vs 10.4 months (HR 0.62; 95% CI 0.49-0.78); interim median OS 32.1 vs 22.8 months (HR 0.68). COMPASSION-16 (N=445; cadonilimab vs placebo plus platinum chemotherapy with or without bevacizumab): median PFS 12.7 vs 8.1 months (HR 0.62); OS HR 0.64, median not reached vs 22.8 months.

  115. 2023 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Blinatumomab added to chemotherapy in infant ALL

    Infants with KMT2A-rearranged ALL have had poor outcomes with chemotherapy alone. In a study of 30 infants, one course of blinatumomab, a drug that links T cells to CD19-bearing leukemia cells, was added to Interfant-06 chemotherapy. Disease-free survival at two years was about 82%, compared with about 49% in earlier Interfant-06 patients.

    Single-arm study, 30 infants with newly diagnosed KMT2A-rearranged ALL: Interfant-06 chemotherapy plus one 28-day post-induction blinatumomab course (15 µg/m2/day). Primary end point, clinically relevant toxic effects: none occurred. 2-year DFS 81.6% (95% CI 60.8-92.0) vs 49.4% (42.5-56.0) in historical Interfant-06 controls; OS 93.3% vs 65.8%. Follow-up at median 4.2 years: 4-year DFS 83.3% vs 44.0%, OS 93.3% vs 60.2%.

  116. 2023 · Treatment · Chronic lymphocytic leukaemia

    Pirtobrutinib: non-covalent BTK inhibitor after covalent BTK failure

    Pirtobrutinib is a BTK blocker that binds reversibly, tested in people whose CLL had stopped responding to earlier BTK drugs. A 2023 study reported responses in about three of four such people, and later randomised trials found longer progression-free survival than standard comparators. The US regulator granted accelerated approval in December 2023 and traditional approval followed in December 2025.

    BRUIN phase 1-2 (CLL/SLL after a BTK inhibitor, n=247): ORR 73.3% (95% CI 67.3 to 78.7), median PFS 19.6 months. CLL-321 (n=238, vs idelalisib-rituximab or bendamustine-rituximab; updated analysis): PFS HR 0.54, median 14 vs 8.7 months; OS HR 1.09. CLL-313 (n=282, untreated, no del(17p), vs bendamustine-rituximab): PFS HR 0.199, 24-month PFS 93.4% vs 70.7%. FDA: accelerated 1 December 2023; fulfilled 3 December 2025; untreated CLL 2 October 2026.

  117. 2023 · Treatment · Colorectal cancer

    FOxTROT: neoadjuvant chemotherapy for locally advanced colon cancer

    In FOxTROT, people with colon cancer growing into or beyond the bowel wall were randomly given six weeks of chemotherapy before surgery and eighteen weeks after, or twenty-four weeks after surgery alone. Fewer in the before-surgery group had residual or returned disease within two years, about seventeen in a hundred against twenty-two. Benefit looked small with mismatch repair deficiency.

    FOxTROT (Morton 2023): 1053 patients (699 NAC, 354 control) with radiologically staged T3-4 N0-2 M0 colon cancer randomised 2:1 to 6 weeks of preoperative oxaliplatin-fluoropyrimidine plus 18 weeks postoperatively, or 24 weeks postoperatively. Residual disease or recurrence within 2 years: 16.9% vs 21.5% (rate ratio 0.72, 95% CI 0.54-0.98, P=0.037); complete resection 94% vs 89%. Panitumumab added no benefit.

  118. 2023 · De-escalation · Colorectal cancer

    PROSPECT: neoadjuvant FOLFOX with selective chemoradiotherapy

    PROSPECT compared chemotherapy first, adding chemoradiotherapy only if the tumour shrank little or chemotherapy had to stop, with standard chemoradiotherapy before surgery, in people with rectal cancer suitable for sphincter-sparing surgery. After about five years, disease-free survival was similar, roughly eight in ten in both groups. Fewer than one in ten given chemotherapy first had radiation before surgery.

    Noninferiority phase 2/3, 1194 randomised (1128 started treatment): neoadjuvant FOLFOX with selective chemoradiotherapy vs chemoradiotherapy, cT2N+/cT3N0/cT3N+ rectal cancer. At median 58 months, DFS hazard ratio 0.92 (90.2% CI 0.74-1.14; P=0.005 for noninferiority, margin 1.29); 5-year DFS 80.8% vs 78.6%; overall survival HR 1.04 (0.74-1.44). Preoperative chemoradiotherapy was given to 9.1% of the FOLFOX group.

  119. 2023 · Treatment · Endometrial cancer

    RUBY: dostarlimab added to carboplatin-paclitaxel, first line

    People with advanced or recurrent endometrial cancer received carboplatin and paclitaxel with either the immune drug dostarlimab or a placebo, then dostarlimab or placebo alone. Cancer took longer to progress with dostarlimab, most clearly in tumours with a mismatch repair deficiency. A later analysis also showed longer survival in the overall group.

    Phase 3, double-blind, 1:1 (N=494): carboplatin-paclitaxel with dostarlimab 500 mg or placebo for 6 cycles, then dostarlimab 1000 mg or placebo. Investigator-assessed PFS at 24 months: dMMR/MSI-H 61.4% vs 15.7% (HR 0.28; 95% CI 0.16-0.50); overall 36.1% vs 18.1% (HR 0.64; 0.51-0.80). Second interim OS: overall HR 0.69 (0.54-0.89); dMMR/MSI-H 0.32 (0.17-0.63); pMMR/MSS 0.79 (0.60-1.04), subgroups with nominal P values.

  120. 2023 · Treatment · Endometrial cancer

    NRG-GY018: pembrolizumab added to chemotherapy, both MMR cohorts

    People with advanced or recurrent endometrial cancer received carboplatin and paclitaxel with either the immune drug pembrolizumab or a placebo. Tumours with and without a mismatch repair deficiency were studied as two separate groups. In both groups cancer took longer to progress with pembrolizumab. Survival results were still immature.

    Phase 3, double-blind, placebo-controlled, 816 enrolled, analysed as separate dMMR and pMMR cohorts; primary endpoint investigator-assessed PFS. dMMR: 12-month PFS 74% vs 38% (HR 0.30; 95% CI 0.19-0.48). pMMR: median PFS 13.1 vs 8.7 months (HR 0.54; 0.41-0.71). Later overall survival was immature: pMMR HR 0.79 (0.53-1.17); dMMR HR 0.55 (0.25-1.19); one-sided nominal P values.

  121. 2023 · Treatment · Endometrial cancer

    DUO-E: durvalumab with or without olaparib, first line

    People with advanced or recurrent endometrial cancer received carboplatin and paclitaxel with placebo, with the immune drug durvalumab, or with durvalumab followed by olaparib. Cancer took longer to progress in both durvalumab groups. Survival data were early. In the United States only durvalumab, for mismatch repair-deficient disease, was approved.

    Phase 3, double-blind, 1:1:1 (N=718): carboplatin-paclitaxel with placebo, durvalumab 1120 mg, or durvalumab plus maintenance olaparib 300 mg. ITT PFS (investigator): durvalumab HR 0.71 (95% CI 0.57-0.89); durvalumab plus olaparib HR 0.55 (0.43-0.69). Exploratory subgroups: dMMR HR 0.42 and 0.41; pMMR HR 0.77 and 0.57. First interim OS (28% maturity): HR 0.77 (0.56-1.07) and 0.59 (0.42-0.83).

  122. 2023 · Understanding · Endometrial cancer

    FIGO 2023: molecular and histological features enter staging

    In 2023 the international gynaecology federation FIGO updated how endometrial cancer is staged. The new system adds tumour type, growth pattern and molecular subtype to how far the cancer has spread, and encourages molecular testing in all endometrial cancers.

    FIGO staging of endometrial cancer, 2023 (FIGO Women's Cancer Committee subcommittee; update of the 2009 system) adds histological type, tumour pattern and molecular classification (POLEmut, MMRd, NSMP, p53abn) to staging, with new substages such as IA1-IA3 and IIA-IIC. In stage I-II disease, p53abn or POLEmut status changes the stage (IICmp53abn, IAmPOLEmut). This is a consensus classification, not a trial report.

  123. 2023 · Treatment · Gastric and gastro-oesophageal junction cancer

    Zolbetuximab for CLDN18.2-positive disease: SPOTLIGHT and GLOW

    In 2023 two trials tested zolbetuximab, an antibody against the claudin 18.2 protein, with first-line chemotherapy in HER2-negative stomach or junction cancers that carry that protein. Both reported that the risk of progression or death was lower, by about a quarter in one and about a third in the other, and that the risk of death was also lower.

    SPOTLIGHT (565 patients, zolbetuximab plus mFOLFOX6 vs placebo plus mFOLFOX6, CLDN18.2-positive, HER2-negative): median PFS 10.61 vs 8.67 months, HR 0.75 (95% CI 0.60 to 0.94), p=0.0066; OS HR 0.75 (0.60 to 0.94), p=0.0053. GLOW (507 patients, with CAPOX): median PFS 8.21 vs 6.80 months, HR 0.687 (0.544 to 0.866); median OS 14.39 vs 12.16 months, HR 0.771 (0.615 to 0.965).

  124. 2023 · Treatment · Glioblastoma

    Vorasidenib delays progression in IDH-mutant grade 2 glioma (INDIGO)

    In 2023 a trial of 331 people with grade 2 IDH-mutant glioma, who had had only surgery, compared vorasidenib, a daily tablet, with a placebo. Time without tumour growth on scans was about 28 months with vorasidenib and 11 months with placebo. This tumour type is not glioblastoma.

    INDIGO (n=331: 168 vorasidenib 40 mg daily, 163 placebo): double-blind phase 3 in residual or recurrent grade 2 IDH-mutant glioma after surgery only. Imaging-based PFS by blinded review: median 27.7 vs 11.1 months, HR 0.39 (95% CI 0.27 to 0.56; P<0.001); time to next intervention HR 0.26 (95% CI 0.15 to 0.43). Grade 3 or higher adverse events 22.8% vs 13.5%.

  125. 2023 · Treatment · Kidney cancer (renal cell carcinoma)

    LITESPARK-005: belzutifan versus everolimus after ICI and TKI (2023)

    Belzutifan was compared with everolimus in people whose kidney cancer had progressed after both an immunotherapy and an antiangiogenic drug. Median time without progression was the same (5.6 months), but more people were progression-free at 18 months and more tumours shrank. Survival did not differ significantly. The FDA approved belzutifan in December 2023.

    LITESPARK-005 (phase 3, open-label, n=746) after checkpoint-inhibitor and antiangiogenic therapy: belzutifan 120 mg vs everolimus 10 mg daily. First interim analysis (median follow-up 18.4 months): median PFS 5.6 months in both arms; 18-month PFS 24.0% vs 8.3%; ORR 21.9% vs 3.5%. FDA page: PFS HR 0.75 (95% CI 0.63-0.90). OS at second interim: 21.4 vs 18.1 months, HR 0.88 (0.73-1.07), not significant. FDA approval 14 December 2023.

  126. 2023 · Treatment · Lung cancer

    Perioperative chemo-immunotherapy: KEYNOTE-671, AEGEAN, CheckMate 77T

    Three trials gave an immune checkpoint inhibitor with platinum chemotherapy before surgery, and the same drug alone afterwards, for operable lung cancer, against chemotherapy plus placebo. In each, the cancer took longer to return or progress and more people had no living cancer at surgery. Survival results differ and are not ranked.

    Three phase 3 trials of perioperative PD-(L)1 inhibitor plus platinum chemotherapy vs chemotherapy plus placebo in resectable NSCLC. KEYNOTE-671 (N=797): 24-month EFS 62.4% vs 40.6% (HR 0.58); 36-month OS 71% vs 64% (HR 0.72). AEGEAN (802 randomised; 740 analysed): EFS HR 0.68 (95% CI 0.53-0.88). CheckMate 77T: 18-month EFS 70.2% vs 50.0% (HR 0.58; 97.36% CI 0.42-0.81).

  127. 2023 · Treatment · Lung cancer

    First-line EGFR combinations: FLAURA2 and MARIPOSA

    Two trials compared newer combinations with osimertinib alone as first treatment for EGFR-mutated advanced lung cancer. Osimertinib plus chemotherapy (FLAURA2) and amivantamab plus lazertinib (MARIPOSA) each delayed progression and later showed longer survival, with more serious side effects than osimertinib alone.

    FLAURA2 (N=557), osimertinib plus platinum-pemetrexed vs osimertinib: PFS HR 0.62 (95% CI 0.49-0.79); final OS median 47.5 vs 37.6 months, HR 0.77 (0.61-0.96). MARIPOSA, amivantamab-lazertinib vs osimertinib (429 each): median PFS 23.7 vs 16.6 months, HR 0.70 (0.58-0.85); OS HR 0.75 (0.61-0.92), 3-year OS 60% vs 51%. Grade 3 or higher adverse events 70% vs 34% (FLAURA2), 80% vs 52% (MARIPOSA).

  128. 2023 · Treatment · Lung cancer

    Tarlatamab: DLL3 T-cell engager for previously treated SCLC

    Tarlatamab is an antibody that links a person's T cells to cells carrying a protein called DLL3. In a phase 2 trial in previously treated small-cell lung cancer, about 4 in 10 people given the 10 mg dose had a tumour response. A later randomised trial found longer median survival than with chemotherapy: 13.6 versus 8.3 months.

    DeLLphi-301 (phase 2, N=220 treated; 10 mg vs 100 mg every 2 weeks): ORR by BICR 40% (97.5% CI 29-52) and 32% (21-44); median PFS 4.9 vs 3.9 months; 9-month OS 68% vs 66%. DeLLphi-304 (phase 3, N=509, tarlatamab 254 vs chemotherapy 255): median OS 13.6 vs 8.3 months (stratified HR 0.60; 95% CI 0.47-0.77; P<0.001; interim analysis). FDA: accelerated approval 16 May 2024; conversion to traditional approval 19 November 2025.

  129. 2023 · Treatment · Melanoma

    SWOG S1801: neoadjuvant-adjuvant versus adjuvant-only pembrolizumab

    This randomised phase 2 trial compared pembrolizumab given before and after surgery with pembrolizumab given only after surgery in people with resectable stage III or IV melanoma. Event-free survival was longer with the before-and-after schedule: about seven in ten were event-free at two years against about half. Follow-up was short.

    Randomised, open-label phase 2 (N=313); clinically detectable, measurable stage IIIB-IVC melanoma amenable to resection. Pembrolizumab 3 doses before surgery plus 15 after (n=154) vs surgery then 18 doses (n=159). Median follow-up 14.7 months: EFS longer with neoadjuvant-adjuvant (P=0.004, log-rank); landmark 2-year EFS 72% (95% CI 64-80) vs 49% (95% CI 41-59). Grade 3 or higher treatment-related adverse events 12% vs 14%.

  130. 2023 · Reversal · Multiple myeloma

    Belantamab mafodotin: withdrawn in 2023, approved again in 2025

    Belantamab mafodotin, an antibody-drug conjugate aimed at BCMA, was approved in the US in 2020 on response rates. Its required follow-up trial did not show longer time without progression than pomalidomide and dexamethasone, and the US licence was withdrawn in 2023. Two later trials of combinations reported longer progression-free survival, and the US approved a combination in 2025.

    DREAMM-2 (randomised phase 2, n=196): ORR 31% (2.5 mg/kg) and 34% (3.4 mg/kg). DREAMM-3 (versus Pd, n=325), primary analysis: median PFS 11.2 versus 7.0 months, HR 1.03 (95% CI 0.72 to 1.47), P=0.56; final analysis PFS HR 0.87 (0.64 to 1.18), OS HR 0.98 (0.73 to 1.30). DREAMM-7 (BVd versus DVd): PFS HR 0.41 (0.31 to 0.53). DREAMM-8 (BPd versus PVd): HR 0.52 (0.37 to 0.73). Ocular events 79% and 89%.

  131. 2023 · Treatment · Neuroblastoma and Wilms tumour

    Eflornithine maintenance to reduce relapse: FDA approval (2023)

    In December 2023 the US regulator approved eflornithine, a tablet, to reduce relapse risk in people with high-risk neuroblastoma who responded to earlier treatment including antibody therapy. The evidence was a single-arm study compared with matched patients from an earlier trial, not a randomized comparison. An advisory committee voted fourteen to six that evidence of improved event-free survival was sufficient.

    NMTRC003B (single-arm phase 2, oral DFMO up to 2 years) vs patient-level ANBL0032 data as external control. Overall: 92 DFMO vs 852 controls, EFS HR 0.50 (95% CI 0.29 to 0.84), OS HR 0.38 (0.19 to 0.76). Propensity-matched 3:1 (90 vs 270): EFS HR 0.48 (0.27 to 0.85), OS HR 0.32 (0.15 to 0.70). FDA approval 13 December 2023 (ODAC vote 14 yes, 6 no).

  132. 2023 · Treatment · Pancreatic cancer

    NAPOLI-3: NALIRIFOX versus nab-paclitaxel plus gemcitabine

    In 770 people with untreated spread pancreatic cancer, a four-drug regimen called NALIRIFOX was compared with nab-paclitaxel plus gemcitabine. Median survival was about 11 months versus about 9 months. Severe (grade 3 or higher) side effects were about equally common. The US regulator approved it in February 2024.

    NAPOLI 3, open-label phase 3: 770 treatment-naive patients with metastatic PDAC, ECOG 0-1; NALIRIFOX (383) vs nab-paclitaxel-gemcitabine (387). Median OS 11.1 (95% CI 10.0-12.1) vs 9.2 months (8.3-10.6); HR 0.83 (95% CI 0.70-0.99; p=0.036). Grade 3 or higher treatment-emergent adverse events 87% vs 86%. FDA approval 13 February 2024.

  133. 2023 · Treatment · Prostate cancer

    Enzalutamide for high-risk biochemical recurrence (EMBARK)

    EMBARK tested enzalutamide in 1,068 men whose prostate cancer had a rising PSA, called biochemical recurrence, with a high risk of progression. At five years, 87.3% of men on enzalutamide plus leuprolide were free of metastasis and alive, against 71.4% on leuprolide alone. The FDA approved this use on 16 November 2023.

    EMBARK (n=1068; phase 3): high-risk biochemical recurrence, PSA doubling time 9 months or less. Enzalutamide plus leuprolide, placebo plus leuprolide, or enzalutamide alone. Primary end point MFS (blinded independent central review); median follow-up 60.7 months. 5-year MFS 87.3% versus 71.4%, HR 0.42 (95% CI 0.30-0.61; P<0.001); enzalutamide alone 80.0%, HR 0.63 (0.46-0.87; P=0.005). The abstract reports no overall survival.

  134. 2023 · Reversal · Thyroid cancer

    NRG/RTOG 0912: pazopanib plus chemoradiotherapy in anaplastic cancer

    The trial report describes anaplastic thyroid cancer as having no standard radiotherapy-based local treatment. A US randomised trial added pazopanib or placebo to paclitaxel plus radiotherapy. Survival was not significantly better with pazopanib (median 5.7 versus 7.3 months). The authors report the approach was feasible and that the data may generate hypotheses.

    NRG/RTOG 0912 (double-blind phase 2; 71 eligible of 89 enrolled): paclitaxel plus IMRT 66 Gy with pazopanib (n=36) vs placebo (n=35). Median OS 5.7 months (95% CI 4.0 to 12.8) vs 7.3 (4.3 to 10.6); HR 0.86 (95% CI 0.52 to 1.43; one-sided log-rank p=0.28). 1-year OS 37.1% vs 29.0%. Grade 3-5 adverse events 88.9% vs 85.3% (p=0.73).

  135. 2023 · Treatment · Thyroid cancer

    LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib

    In a randomised trial of 291 people with advancing RET-mutant medullary thyroid cancer, selpercatinib delayed progression for longer than the doctor's choice of cabozantinib or vandetanib, in an interim analysis. At one year about 87 in 100 on selpercatinib had no progression, against about 66 in 100 on the older drugs, and fewer people stopped treatment because of side effects.

    LIBRETTO-531, phase 3, open-label: 291 patients with progressive, kinase inhibitor-naive RET-mutant MTC; selpercatinib vs physician's choice of cabozantinib or vandetanib. Interim analysis, median follow-up 12 months: median PFS (blinded central review) not reached vs 16.8 months (95% CI 12.2-25.1), HR 0.28 (0.16-0.48), P<0.001; 12-month PFS 86.8% vs 65.7%. TFFS HR 0.25 (0.15-0.42). ORR 69.4% vs 38.8%. Dose reduction 38.9% vs 77.3%.

  136. 2023 · Reversal · Thyroid cancer

    Pralsetinib in RET thyroid cancer; MTC indication withdrawn 2023

    Pralsetinib, a RET-targeted pill, shrank tumours in roughly 56 to 77 of every 100 people with RET-mutant medullary thyroid cancer in a single-arm study, and gained US accelerated approval in 2020. In 2023 that use was withdrawn at the sponsor's request after the confirmatory trial proved hard to run, not, the sponsor said, because of new safety or efficacy data.

    ARROW thyroid cohorts (phase 1-2, single-arm, pralsetinib 400 mg daily; masked central review). Interim: ORR 71% (15 of 21) treatment-naive and 60% (33 of 55) cabozantinib/vandetanib-pretreated RET-mutant MTC; 89% (8 of 9) RET fusion-positive thyroid cancer. Update (cutoff 18 October 2021): ORR 77.4% (62 patients), 55.7% (61), 90.9% (22). Accelerated approval 1 December 2020; MTC indication removed 20 July 2023 at sponsor request; phase 3 AcceleRET-MTC withdrawn, no patients enrolled.

  137. 2024 · Reversal · Bladder cancer

    Sacituzumab govitecan urothelial indication withdrawn

    In 2021 the FDA granted accelerated approval to sacituzumab govitecan for advanced bladder cancer after platinum chemotherapy and immunotherapy, based on a single-arm study in which about 27 in 100 people responded. In 2024 the indication was withdrawn at the sponsor's request; the FDA letter says the confirmatory randomised trial did not confirm clinical benefit.

    TROPHY-U-01 cohort 1 (phase 2, single-arm, n=113): ORR 27% (95% CI 19.5-36.6), median DOR 7.2 months, median OS 10.9 months. TROPiCS-04 (phase 3, N=711): median OS 10.3 vs 9.0 months (HR 0.86; 95% CI 0.73-1.02; P=0.087); primary endpoint not met. FDA accelerated approval 13 April 2021; voluntary withdrawal 22 November 2024.

  138. 2024 · Treatment · Bladder cancer

    NIAGARA: durvalumab added to neoadjuvant gemcitabine-cisplatin

    In people with muscle-invasive bladder cancer who could receive cisplatin, adding the immunotherapy durvalumab before and after surgery to standard chemotherapy was tested against chemotherapy alone. At two years, 68% were event-free versus 60%, and 82% were alive versus 75%. The FDA approved the regimen in March 2025.

    NIAGARA (phase 3, n=1063, cisplatin-eligible MIBC): neoadjuvant durvalumab plus gemcitabine-cisplatin, cystectomy, adjuvant durvalumab vs gemcitabine-cisplatin then cystectomy alone. 24-month EFS 67.8% vs 59.8% (HR 0.68, 95% CI 0.56-0.82, P<0.001); 24-month OS 82.2% vs 75.2% (HR 0.75, 0.59-0.93, P=0.01). Cystectomy performed in 88.0% vs 83.2%; grade 3 or 4 treatment-related adverse events 40.6% vs 40.9%. FDA approval 28 March 2025.

  139. 2024 · Treatment · Cervical cancer

    KEYNOTE-A18: pembrolizumab added to chemoradiation (FDA Jan 2024)

    In a large trial of women with newly diagnosed, high-risk locally advanced cervical cancer, adding the immunotherapy pembrolizumab to chemoradiation, and continuing it afterwards, lowered the risk of progression. A later analysis found more women alive at three years. The US regulator approved the combination in January 2024.

    ENGOT-cx11/GOG-3047/KEYNOTE-A18 (N=1060, double-blind): pembrolizumab or placebo with cisplatin chemoradiotherapy, then maintenance. First interim analysis: 24-month PFS 68% vs 57%, HR 0.70 (95% CI 0.55 to 0.89; p=0.0020). Second interim analysis: 36-month OS 82.6% vs 74.8%, HR 0.67 (0.50 to 0.90; p=0.0040). Grade 3 or higher adverse events 78% vs 70%.

  140. 2024 · De-escalation · Cervical cancer

    SHAPE: simple hysterectomy for low-risk early cervical cancer

    In a trial of women with small, low-risk cervical cancers (2 cm or less, limited invasion), a simple hysterectomy with lymph-node assessment was not worse than a radical hysterectomy for pelvic recurrence at three years. Urinary leakage and bladder-emptying problems were less common after the simpler operation.

    SHAPE (N=700; radical vs simple hysterectomy with lymph-node assessment; lesions 2 cm or less with limited stromal invasion): 3-year pelvic recurrence 2.17% radical vs 2.52% simple, difference 0.35 points (90% CI -1.62 to 2.32; non-inferiority margin 4 points); median follow-up 4.5 years. Urinary incontinence beyond 4 weeks 11.0% vs 4.7% (P=0.003); urinary retention beyond 4 weeks 9.9% vs 0.6% (P<0.001).

  141. 2024 · Treatment · Cervical cancer

    INTERLACE: weekly induction chemotherapy before chemoradiation

    In a trial of 500 women with locally advanced cervical cancer, six weeks of weekly carboplatin and paclitaxel before standard chemoradiation was associated with better outcomes than chemoradiation alone: about 72 in 100 versus 64 in 100 were alive without progression at five years, and 80 versus 72 were alive. More serious side effects occurred with induction.

    INTERLACE (phase 3, N=500, ITT): six weekly carboplatin-paclitaxel doses before cisplatin chemoradiotherapy vs chemoradiotherapy alone. Median follow-up 67 months: 5-year PFS 72% vs 64%, HR 0.65 (95% CI 0.46 to 0.91; p=0.013); 5-year OS 80% vs 72%, HR 0.60 (0.40 to 0.91; p=0.015). Grade 3 or greater adverse events 59% vs 48%.

  142. 2024 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Blinatumomab added to chemotherapy in standard-risk B-ALL

    In a large Children's Oncology Group trial of children with newly diagnosed standard-risk B-cell ALL, adding two cycles of the antibody blinatumomab to chemotherapy was followed by better disease-free survival at three years: about 96 in 100 versus about 88 in 100. Infections were more common with blinatumomab in one subgroup. This is an early interim analysis.

    COG AALL1731, phase 3: NCI standard-risk B-ALL with average or higher relapse risk; chemotherapy alone (722) versus chemotherapy plus two 28-day blinatumomab cycles (718). First interim analysis, median follow-up 2.5 years: 3-year DFS 96.0% versus 87.9% (RMST difference 72 days, 95% CI 36 to 108; P<0.001, stratified log-rank). Average relapse risk 97.5% versus 90.2%; higher risk 94.1% versus 84.8%. Randomisation stopped early on committee recommendation.

  143. 2024 · Treatment · Chronic myeloid leukemia

    ASC4FIRST: asciminib in newly diagnosed chronic-phase CML

    In 2024 a trial of 405 adults with newly diagnosed chronic-phase CML compared asciminib, which acts on BCR-ABL1 at a different site from older drugs, with a TKI chosen by the treating doctor. At 48 weeks about two in three on asciminib and about half on the comparators had a major molecular response. US approval is accelerated, pending confirmation.

    ASC4FIRST (NCT04971226): open-label phase 3, 405 adults, asciminib 80 mg daily vs investigator-selected TKI (1:1). MMR at week 48: 67.7% vs 49.0% (difference 18.9 percentage points, 95% CI 9.6-28.2; P<0.001); imatinib stratum 69.3% vs 40.2%. Second-generation TKI stratum: 66.0% vs 57.8% (difference 8.2, 95% CI -5.1 to 21.5), not a primary objective. Week 96: 74.1% vs 52.0%.

  144. 2024 · Treatment · Colorectal cancer

    NICHE-2: neoadjuvant nivolumab plus ipilimumab for dMMR colon cancer

    In NICHE-2, 115 people with locally advanced colon cancer with mismatch repair deficiency had nivolumab and ipilimumab before surgery. Nearly all had surgery on time. Among 111 assessed, about two in three had no viable tumour left, and none had recurrence by a median of 26 months. It was a single-group study without a comparison arm.

    NICHE-2 (Chalabi 2024): phase 2, single-arm, 115 patients with untreated locally advanced dMMR colon cancer given neoadjuvant nivolumab plus ipilimumab. Timely surgery in 113 (98%; 97.5% CI 93-100). In 111 patients in the efficacy analysis, pathological response in 109 (98%; 95% CI 94-100), major pathological response in 105 (95%), pCR in 75 (68%). Grade 3-4 immune-related adverse events in 5 (4%). Median follow-up 26 months: no recurrence; 3-year DFS not reported in the abstract.

  145. 2024 · Treatment · Colorectal cancer

    BREAKWATER: first-line encorafenib, cetuximab and chemotherapy

    Bowel cancers with a BRAF V600E change have had limited benefit from standard first-line chemotherapy. In a randomised trial, adding encorafenib and cetuximab to the chemotherapy mFOLFOX6 shrank more tumours, delayed progression and lengthened survival compared with standard care. US approval was provisional (accelerated) in 2024; in 2026 the regulator recorded its follow-up requirement as fulfilled.

    Open-label phase 3 trial, previously untreated BRAF V600E-mutant metastatic colorectal cancer: encorafenib + cetuximab + mFOLFOX6 vs standard care (chemotherapy with or without bevacizumab). ORR by blinded central review 60.9% vs 40.0% (odds ratio 2.443, one-sided P=0.0008). PFS median 12.8 vs 7.1 months (HR 0.53, 95% CI 0.41-0.68). Interim OS median 30.3 vs 15.1 months (HR 0.49, 95% CI 0.38-0.63).

  146. 2024 · Treatment · Colorectal cancer

    CheckMate 8HW: nivolumab plus ipilimumab in MSI-H/dMMR mCRC

    Colorectal cancers with faulty DNA mismatch repair can respond to immune checkpoint drugs. In a randomised trial, people given nivolumab plus ipilimumab as their first treatment stayed free of progression longer than those given chemotherapy. A second report found they also stayed free of progression longer than with nivolumab alone. In 2025 the US approvals became full approvals.

    Open-label phase 3 trial, 2:2:1 randomisation (nivolumab + ipilimumab, nivolumab, chemotherapy) in MSI-H/dMMR metastatic colorectal cancer. First line (NEJM 2024): 24-month PFS 72% vs 14% for nivolumab + ipilimumab vs chemotherapy (P<0.001; centrally confirmed, n=255). All lines (Lancet 2025): nivolumab + ipilimumab vs nivolumab, PFS HR 0.62 (95% CI 0.48-0.81; P=0.0003).

  147. 2024 · Reversal · Endometrial cancer

    KEYNOTE-B21: adjuvant pembrolizumab, no DFS gain overall

    In women with newly diagnosed high-risk endometrial cancer, pembrolizumab or a placebo was added to chemotherapy after surgery. Across all women, disease-free survival did not differ. In a planned subgroup of tumours with mismatch repair deficiency the pembrolizumab group fared better, but this was not a formal test and follow-up is early.

    Randomised double-blind phase 3 (1095 randomised): pembrolizumab 200 mg or placebo every 3 weeks for six cycles with carboplatin-paclitaxel, then 400 mg or placebo every 6 weeks for six cycles. Interim analysis (data cut-off 4 March 2024): DFS HR 1.02 (95% CI 0.79-1.32; p=0.570); 2-year DFS 75% vs 76%. dMMR (n=281) HR 0.31 (0.14-0.69); pMMR (n=814) HR 1.20 (0.91-1.57). Grade 3 or worse adverse events 71% vs 63%.

  148. 2024 · Treatment · Glioblastoma

    Dordaviprone gets accelerated approval for H3 K27M midline glioma

    ONC201 (dordaviprone), a capsule, was studied in 50 people with recurrent H3 K27M-mutant diffuse midline glioma. About one in five had a tumour response on scans. In August 2025 US regulators gave it accelerated approval and required a randomised trial to confirm benefit. This is not glioblastoma.

    Integrated analysis of 50 patients (46 adult, 4 paediatric) with recurrent H3 K27M-mutant diffuse midline glioma given single-agent ONC201 across trials and an expanded access protocol: ORR by RANO-HGG 20.0% (95% CI 10.0 to 33.7), median DOR 11.2 months, median time to response 8.3 months; combined RANO-HGG/LGG ORR 30.0% (95% CI 17.9 to 44.6). FDA accelerated approval 6 August 2025.

  149. 2024 · Treatment · Hodgkin lymphoma

    S1826: nivolumab plus AVD versus BV plus AVD

    In people aged 12 and older with newly diagnosed advanced Hodgkin lymphoma, nivolumab (a PD-1 checkpoint antibody) plus chemotherapy was compared with brentuximab vedotin plus the same chemotherapy. At two years about 92 in 100 people on the nivolumab regimen had no progression or death, compared with 83 in 100 on the other.

    Phase 3 (994 randomised; 970 in ITT efficacy population), stage III or IV classic HL, age 12 years or older: N+AVD versus BV+AVD, primary endpoint PFS. Second interim analysis (median follow-up 12.1 months): HR 0.48 (99% CI 0.27 to 0.87; P=0.001). Repeated analysis (median follow-up 2.1 years): 2-year PFS 92% versus 83%, HR 0.45 (95% CI 0.30 to 0.65).

  150. 2024 · Treatment · Hodgkin lymphoma

    HD21: BrECADD versus escalated BEACOPP

    For adults up to 60 with advanced Hodgkin lymphoma, a PET-guided regimen containing brentuximab vedotin (BrECADD) caused fewer serious treatment-related problems than escalated BEACOPP (42 in 100 versus 59 in 100). Disease control was at least as good: about 94 in 100 versus 91 in 100 were free of progression at four years.

    Open-label phase 3, adults aged 60 years or younger with advanced-stage classic HL (1482 in ITT): PET-guided BrECADD versus eBEACOPP. Treatment-related morbidity 42% versus 59% (RR 0.72, 95% CI 0.65 to 0.80; P<0.0001). Median follow-up 48 months: PFS HR 0.66 (95% CI 0.45 to 0.97; P=0.035); 4-year PFS 94.3% versus 90.9%; 4-year OS 98.6% versus 98.2%.

  151. 2024 · Treatment · Lung cancer

    LAURA: osimertinib after chemoradiotherapy, stage III

    In LAURA, people with unresectable stage III EGFR-mutated lung cancer whose disease had not progressed after chemotherapy plus radiotherapy took osimertinib or placebo. Median time to progression or death was 39.1 months with osimertinib and 5.6 months with placebo. Survival data were still immature.

    LAURA (N=216; osimertinib 143, placebo 73), double-blind, unresectable stage III EGFR-mutated NSCLC without progression after chemoradiotherapy. BICR median PFS 39.1 vs 5.6 months, HR 0.16 (95% CI 0.10-0.24; P<0.001); 12-month PFS 74% vs 22%. Interim OS (20% maturity): 36-month OS 84% vs 74%, HR 0.81 (0.42-1.56; P=0.53). Grade 3 or higher adverse events 35% vs 12%.

  152. 2024 · Treatment · Lung cancer

    ALINA: adjuvant alectinib in resected ALK-positive disease

    After surgery for ALK-positive lung cancer, one trial compared two years of an ALK-blocking pill, alectinib, with standard platinum chemotherapy. About 94 in 100 people on alectinib were alive and free of recurrence at two years, against about 64 in 100 on chemotherapy. Overall survival data were not yet mature.

    Phase 3 ALINA (n=257, 1:1) in completely resected ALK-positive stage IB (4 cm or larger), II or IIIA NSCLC: alectinib 600 mg twice daily for 24 months versus four cycles of platinum-based chemotherapy. Two-year DFS 93.8% vs 63.0% in stage II-IIIA (HR 0.24, 95% CI 0.13-0.45, P<0.001); ITT 93.6% vs 63.7% (HR 0.24, 0.13-0.43). CNS disease-free survival HR 0.22 (0.08-0.58). Overall survival immature.

  153. 2024 · Treatment · Lung cancer

    ADRIATIC: durvalumab after chemoradiotherapy, limited-stage SCLC

    Some people with limited-stage small-cell lung cancer have no sign of progression after chemotherapy given together with chest radiotherapy. In a randomised trial's first planned interim analysis, durvalumab every four weeks for up to two years afterwards was followed by longer median survival than placebo (55.9 versus 33.4 months), with similar rates of serious (grade 3 or 4) side effects.

    ADRIATIC (phase 3, double-blind; durvalumab 264 vs placebo 266, up to 24 months after concurrent platinum-based chemoradiotherapy without progression). First planned interim analysis: median OS 55.9 vs 33.4 months (HR 0.73; 98.321% CI 0.54-0.98; P=0.01); median PFS 16.6 vs 9.2 months (HR 0.76; 97.195% CI 0.59-0.98; P=0.02). Grade 3 or 4 adverse events 24.4% vs 24.2%. FDA approved single-agent durvalumab on 4 December 2024.

  154. 2024 · Treatment · Melanoma

    NADINA: neoadjuvant ipilimumab plus nivolumab in stage III (2024)

    In NADINA, a phase 3 trial of people with stage III melanoma that could be removed by surgery, two doses of ipilimumab plus nivolumab before surgery (with more treatment afterwards only for those without a major response) were followed by longer event-free survival than surgery followed by 12 cycles of nivolumab. Follow-up was short, a median of about ten months.

    Phase 3, randomised; resectable macroscopic stage III melanoma (N=423): two cycles of neoadjuvant ipilimumab plus nivolumab, surgery, and adjuvant therapy only for partial response or nonresponse, vs surgery then 12 cycles of adjuvant nivolumab. Median follow-up 9.9 months: 12-month EFS 83.7% vs 57.2% (HR 0.32; 99.9% CI 0.15-0.66; P<0.001). Major pathological response 59.0%. Grade 3 or higher treatment-related adverse events 29.7% vs 14.7%.

  155. 2024 · Treatment · Melanoma

    Individualised mRNA neoantigen therapy plus pembrolizumab: KEYNOTE-942

    In KEYNOTE-942, a phase 2 trial of 157 people with resected high-risk melanoma, adding an individualised mRNA neoantigen therapy (mRNA-4157, also called V940 or intismeran) to pembrolizumab was followed by fewer recurrences than pembrolizumab alone. The hazard ratio interval included 1 (two-sided P=0.053). A phase 3 trial has been announced; results are unpublished.

    Open-label randomised phase 2b (N=157, 2:1): mRNA-4157 plus pembrolizumab (n=107) vs pembrolizumab (n=50), resected stage IIIB-IV cutaneous melanoma. RFS HR 0.561 (95% CI 0.309-1.017; two-sided P=0.053); events 22% vs 40%; 18-month RFS 79% vs 62%. Descriptive 5-year update: RFS HR 0.510 (95% CI 0.294-0.887), DMFS HR 0.411 (95% CI 0.200-0.843), OS HR 0.471 (95% CI 0.165-1.345).

  156. 2024 · Treatment · Pancreatic cancer

    Zenocutuzumab: pancreatic-cancer indication for NRG1 gene fusions

    NRG1 gene fusions are rare drivers of pancreatic cancer. In a single-group study, 15 of 36 pancreatic cancer patients with measurable disease responded to the antibody zenocutuzumab. The US regulator gave it accelerated approval in December 2024 for NRG1 fusion-positive pancreatic and lung cancer after prior therapy.

    eNRGy, single-arm phase 2 (204 treated, 12 tumour types, NRG1 fusion-positive): zenocutuzumab 750 mg every 2 weeks. Pancreatic cancer ORR 15/36 (42%; 95% CI 25-59); all tumours ORR 30% (95% CI 23-37; n=158), median DOR 11.1 months, median PFS 6.8 months. FDA accelerated approval 4 December 2024 (NSCLC and pancreatic adenocarcinoma after prior systemic therapy).

  157. 2024 · Reversal · Pancreatic cancer

    NORPACT-1: neoadjuvant FOLFIRINOX versus upfront surgery

    NORPACT-1, a randomised phase 2 trial in four Nordic countries, compared four cycles of FOLFIRINOX before surgery with surgery first in resectable pancreatic head cancer. About 60 in 100 were alive at 18 months with FOLFIRINOX first against 73 in 100 with surgery first. The authors did not find a survival benefit from the neoadjuvant approach.

    NORPACT-1 (Labori 2024): randomised phase 2, 140 patients with resectable pancreatic head cancer (77 neoadjuvant FOLFIRINOX, 63 upfront surgery), adjuvant chemotherapy in both. Primary endpoint OS at 18 months, ITT: 60% (95% CI 49-71) vs 73% (62-84), p=0.032. Median OS 25.1 vs 38.5 months, HR 1.52 (95% CI 1.00-2.33), log-rank p=0.050. Resection 82% vs 89%. Grade 3+ events 58% vs 40%.

  158. 2024 · Treatment · Prostate cancer

    Darolutamide plus ADT without docetaxel (ARANOTE)

    ARANOTE tested darolutamide added to hormone therapy, without chemotherapy, in 669 men with metastatic hormone-sensitive prostate cancer. The hazard ratio for radiological progression or death was 0.54 against placebo plus hormone therapy. Overall survival results at that point were described as suggestive of benefit. The FDA approved this use on 3 June 2025.

    ARANOTE (phase 3, 2:1, n=669): darolutamide 600 mg twice daily or placebo with ADT, without docetaxel. At the primary cutoff (7 June 2024): rPFS HR 0.54 (95% CI 0.41-0.71; P<0.0001) with consistent benefit in high- and low-volume disease; OS HR 0.81 (0.59-1.12); time to metastatic castration-resistant disease HR 0.40 (0.32-0.51). Discontinuation for adverse events 6.1% versus 9.0%.

  159. 2024 · Treatment · Prostate cancer

    177Lu-PSMA-617 before taxane chemotherapy (PSMAfore)

    In men with PSMA-positive metastatic castration-resistant prostate cancer who had progressed on one hormonal drug and not yet had chemotherapy, a PSMA-targeted radioactive drug delayed progression on imaging more than switching hormonal drugs: about 12 versus 6 months. Final survival did not differ, and 60% of the comparison group crossed over to the radioligand.

    PSMAfore (phase 3, open-label, N=468): taxane-naive, PSMA-positive mCRPC progressing on one ARPI; 177Lu-PSMA-617 vs change of ARPI. rPFS median 9.30 vs 5.55 months (HR 0.41; 95% CI 0.29-0.56); updated 11.60 vs 5.59 months (HR 0.49; 0.39-0.61). Final OS 24.48 vs 23.13 months (ITT HR 0.91; 0.72-1.14; P=0.20), with 60.3% of the control arm crossing over.

  160. 2024 · Detection · Prostate cancer

    Screening follow-up: CAP (15-year) and ERSPC (23-year)

    Longer follow-up of the European screening trial, now 23 years, still showed fewer prostate cancer deaths in the screening group, alongside more cancers diagnosed. A UK trial offering a single PSA test found no clear difference at 10 years and a small reduction in deaths at 15 years. In both, the absolute difference was well under one percentage point.

    ERSPC core age group (n=162,236; median 23 years): prostate cancer mortality rate ratio 0.87 (95% CI 0.80-0.95), absolute risk reduction 0.22%; 456 men invited and 12 diagnosed per death averted. CAP (single PSA invitation, men aged 50-69, primary care practices): rate ratio 0.96 (0.85-1.08) at 10 years; 0.92 (0.85-0.99) at 15 years, cumulative risk of prostate cancer death 0.69% vs 0.78%; all-cause mortality rate ratio 0.97 (0.94-1.01).

  161. 2024 · Treatment · Sarcoma and GIST

    SU2C-SARC032: pembrolizumab added to radiotherapy before surgery

    In a randomised trial of people with stage III sarcoma of the arm or leg (undifferentiated pleomorphic sarcoma, or dedifferentiated or pleomorphic liposarcoma), adding the immunotherapy pembrolizumab to radiotherapy and surgery was linked to longer disease-free survival: 67% versus 52% at two years. Grade 3 or higher side effects were more common (56% versus 31%).

    Open-label randomised trial (registered as phase 2; 143 randomised; modified ITT n=127, median follow-up 43 months): preoperative radiotherapy then surgery (n=63) vs preoperative pembrolizumab with radiotherapy, surgery and adjuvant pembrolizumab (n=64). DFS (primary): HR 0.61 (90% CI 0.39-0.96; one-sided log-rank p=0.035); 2-year DFS 52% vs 67% (90% CI 42-64 and 58-78). Grade 3 or higher adverse events 31% vs 56%.

  162. 2025 · Treatment · Bladder cancer

    KEYNOTE-905/EV-303: EV plus pembrolizumab around cystectomy

    For people with muscle-invasive bladder cancer who could not or chose not to have cisplatin chemotherapy, enfortumab vedotin plus pembrolizumab before and after surgery was compared with surgery alone. At two years, 75% were event-free versus 39%, and 80% were alive versus 63%. The FDA approved the combination for this group in November 2025.

    KEYNOTE-905/EV-303 (phase 3; 344 randomised: 170 EV-pembrolizumab, 174 surgery alone; MIBC ineligible for or declining cisplatin). Median follow-up 25.6 months. 2-year EFS 74.7% vs 39.4% (HR 0.40, 95% CI 0.28-0.57); OS 79.7% vs 63.1% (HR 0.50, 0.33-0.74); pCR 57.1% vs 8.6%. Grade 3 or higher adverse events 71.3% vs 45.9%. FDA approval 21 November 2025 (cisplatin-ineligible).

  163. 2025 · Treatment · Bladder cancer

    TAR-200 for BCG-unresponsive high-risk NMIBC

    TAR-200 is an intravesical drug-releasing system that delivers gemcitabine into the bladder. In a phase 2 study of people with carcinoma in situ that no longer responded to BCG, about four in five of those given TAR-200 alone had a complete response. The US regulator approved it, as Inlexzo, in September 2025.

    SunRISe-1 (phase IIb, parallel cohorts, no statistical comparison between them), BCG-unresponsive high-risk NMIBC. CIS: complete response 82.4% (95% CI 72.6 to 89.8) with TAR-200 alone, median duration 25.8 months; 67.9% with cetrelimab added; 46.4% with cetrelimab alone. Papillary only (TAR-200 alone): 12-month DFS 70.2% (95% CI 51.6 to 82.8). Grade 3 or worse treatment-related adverse events 12.9% (TAR-200 alone, CIS). FDA approval 9 September 2025.

  164. 2025 · Treatment · Breast cancer

    DESTINY-Breast09: T-DXd plus pertuzumab in first-line therapy

    In a first-line trial for HER2-positive metastatic breast cancer, trastuzumab deruxtecan plus pertuzumab was compared with a taxane, trastuzumab and pertuzumab. Progression took longer with the new combination, and the US regulator approved it in December 2025. Lung inflammation, including two deaths, was reported.

    Phase 3 (1157 enrolled), 1:1:1, first-line HER2-positive metastatic disease. Interim analysis (cutoff 26 February 2025): trastuzumab deruxtecan plus pertuzumab (383 patients) vs THP (387): median PFS (blinded central review) 40.7 vs 26.9 months (HR 0.56; 95% CI 0.44 to 0.71; P<0.00001). Confirmed response 85.1% vs 78.6%. Adjudicated drug-related ILD 12.1% vs 1.0%. The trastuzumab deruxtecan plus placebo arm remained blinded.

  165. 2025 · Treatment · Breast cancer

    ADCs reach first-line metastatic TNBC (ASCENT-03/-04, TROPION-02)

    Three recent trials tested antibody-drug conjugates against chemotherapy as the first treatment for advanced triple-negative breast cancer. Two drugs delayed progression for people who could not receive PD-1/PD-L1 immunotherapy, and sacituzumab govitecan with pembrolizumab did so in PD-L1-positive disease. The groups and comparators differ, so the results should not be set side by side.

    Three phase 3 trials, first-line advanced TNBC. ASCENT-03 (N=558; not candidates for PD-(L)1 inhibitors): PFS 9.7 vs 6.9 months, sacituzumab govitecan vs chemotherapy (HR 0.62; 95% CI 0.50-0.77). ASCENT-04 (N=443; PD-L1-positive): with pembrolizumab, PFS 11.2 vs 7.8 months (HR 0.65; 95% CI 0.51-0.84). TROPION-Breast02 (N=644; immunotherapy not an option): PFS 10.8 vs 5.6 months (HR 0.57); OS 23.7 vs 18.7 months (HR 0.79; 95% CI 0.64-0.98).

  166. 2025 · Treatment · Chronic lymphocytic leukaemia

    AMPLIFY: fixed-duration acalabrutinib-venetoclax vs chemoimmunotherapy

    AMPLIFY compared two fixed-length regimens built on acalabrutinib and venetoclax with chemoimmunotherapy in fit people with untreated CLL. At three years, about three in four on acalabrutinib plus venetoclax were free of progression, versus about two in three on chemoimmunotherapy. The US regulator approved the pair in February 2026.

    AMPLIFY (open-label phase 3; 867 randomised; fit patients without 17p deletion or TP53 mutation): acalabrutinib-venetoclax vs FCR or BR, BICR-assessed PFS HR 0.65 (95% CI 0.49 to 0.87; P=0.004); 36-month PFS 76.5% vs 66.5% at median follow-up 40.8 months; 83.1% with the obinutuzumab triplet (P<0.001 vs chemoimmunotherapy). Estimated 36-month OS 94.1%, 87.7% and 85.9%.

  167. 2025 · Today · Chronic myeloid leukemia

    European LeukemiaNet recommendations, 2006 to 2025

    European LeukemiaNet, a network of CML specialists, has issued five versions of its treatment recommendations; this entry follows 2006, 2013, 2020 and 2025. They track the shift from imatinib alone, judged mainly by blood and chromosome tests, to a choice of several drugs, molecular monitoring and, for selected people, a planned attempt to stop treatment.

    ELN expert-panel recommendations. 2006: imatinib 400 mg daily preferred initial treatment; failure defined by haematologic and cytogenetic response. 2013: imatinib, nilotinib or dasatinib; BCR-ABL1 International Scale milestones at 3, 6 and 12 months. 2020: lists bosutinib first-line; ELTS score; discontinuation may be considered. 2025: dose reduction rather than switching for toxicity; treatment discontinuation guidance; six TKIs approved first-line.

  168. 2025 · De-escalation · Endometrial cancer

    PORTEC-4a: molecular profile guides adjuvant treatment

    Women with early endometrial cancer at high-intermediate risk were randomly assigned to standard vaginal radiotherapy or to treatment chosen by the tumour's molecular profile: observation, vaginal radiotherapy or pelvic radiotherapy. Vaginal recurrence was low in both groups at five years, and nearly half the women in the profile group were observed without further treatment.

    Open-label non-inferiority phase 3 (569 enrolled; 564 analysed: 367 molecular-profile, 197 standard vaginal brachytherapy). Favourable profile observed, intermediate given brachytherapy, unfavourable given pelvic RT. 5-year vaginal recurrence 4.5% (95% CI 2.23-6.76) vs 1.6% (0.00-3.32); HR 2.71 (0.79-9.34); upper bound of one-sided CI of the difference 5.3% vs margin 7.0% (p=0.005). Favourable profile: 4.1% vs 0.9%.

  169. 2025 · Treatment · Gastric and gastro-oesophageal junction cancer

    MATTERHORN: perioperative durvalumab plus FLOT, and KEYNOTE-585

    Adding the immunotherapy drug durvalumab to FLOT chemotherapy before and after surgery improved event-free survival in a randomised trial of operable stomach or junction cancer, and the US regulator approved it in 2025. A trial of another drug, pembrolizumab, with chemotherapy reported less clear results.

    MATTERHORN (948 randomised, durvalumab or placebo with FLOT): primary endpoint EFS, 2-year EFS 67.4% vs 58.5%, HR 0.71 (95% CI 0.58-0.86; P<0.001); pCR 19.2% vs 7.2%; final OS HR 0.78 (0.63-0.96; p=0.021). KEYNOTE-585 final analysis (main cohort, 804): median OS 71.8 vs 55.7 months, HR 0.86 (0.71-1.06); EFS HR 0.81 (0.67-0.98; cohort not stated).

  170. 2025 · Treatment · Head and neck cancer

    KEYNOTE-689: perioperative pembrolizumab for resectable disease

    For people with head and neck cancer that could be removed by surgery, two doses of pembrolizumab before surgery and fifteen afterwards, alongside the usual radiotherapy, were compared with usual care alone. At three years, about 58 in 100 people were free of progression, recurrence or death with pembrolizumab, compared with about 46 in 100 with usual care.

    Open-label phase 3 (N=714): resectable locally advanced HNSCC; 2 cycles of neoadjuvant and 15 of adjuvant pembrolizumab plus standard care (surgery, adjuvant radiotherapy with or without cisplatin) vs standard care. First interim analysis, median follow-up 38.3 months: 36-month EFS 59.8% vs 45.9% in CPS 10 or more (HR 0.66; 95% CI 0.49-0.88), 58.2% vs 44.9% in CPS 1 or more (HR 0.70), 57.6% vs 46.4% in the total population (HR 0.73; 95% CI 0.58-0.92).

  171. 2025 · Treatment · Head and neck cancer

    NIVOPOSTOP: nivolumab added to postoperative cisplatin-radiotherapy

    After surgery for head and neck cancer with features that raise the risk of relapse, people had cisplatin chemotherapy with radiotherapy, with or without the immune drug nivolumab. Relapse or death was less likely with nivolumab, and grade 4 side effects related to treatment were more common (about 10 in 100 people compared with 5 in 100).

    Open-label phase 3, N=680 randomised 1:1 (efficacy analysis of 666 assigned up to cutoff): resected SCCHN with at least one high-risk pathological feature; cisplatin 100 mg per square metre and radiotherapy 66 Gy with or without nivolumab. Median follow-up 30.3 months. Investigator-assessed DFS HR 0.76 (95% CI 0.60-0.98; stratified log-rank P=0.034). Treatment-related grade 4 adverse events 10% vs 5%.

  172. 2025 · Treatment · Hepatocellular carcinoma

    TACE plus immunotherapy: EMERALD-1 and LEAP-012 (PFS)

    Two randomised trials added immunotherapy-based drug combinations to chemoembolisation for liver cancer that could not be removed by surgery. Median time without progression was about 15 versus 8 months in one trial and about 15 versus 10 months in the other. Neither had shown a significant overall survival difference at the analyses reported.

    EMERALD-1 (N=616; TACE + durvalumab + bevacizumab vs TACE + placebo): BICR median PFS 15.0 vs 8.2 months, HR 0.77 (95% CI 0.61-0.98; p=0.032); durvalumab alone HR 0.94 (95% CI 0.75-1.19). LEAP-012 (N=480; TACE + lenvatinib + pembrolizumab vs dual placebo): median PFS 14.6 vs 10.0 months, HR 0.66 (95% CI 0.51-0.84); interim OS HR 0.80 (95% CI 0.57-1.11; one-sided p=0.087).

  173. 2025 · Treatment · Hepatocellular carcinoma

    CheckMate 9DW: first-line nivolumab plus ipilimumab

    Nivolumab plus ipilimumab was compared with lenvatinib or sorafenib in 668 people with liver cancer who had not had drug treatment. Median survival was about 24 months with the combination and about 21 months with the comparison drugs. The FDA approved the combination as first-line treatment in April 2025.

    CheckMate 9DW (open-label phase 3, N=668, no prior systemic therapy, Child-Pugh 5 or 6): nivolumab plus ipilimumab (n=335) vs lenvatinib or sorafenib (n=333). Preplanned interim analysis, median follow-up 35.2 months: median OS 23.7 vs 20.6 months, HR 0.79 (95% CI 0.65-0.96; P=0.018); OS 49% vs 39% at 24 months, 38% vs 24% at 36 months. Curves crossed early (HR 1.65 for the first 6 months).

  174. 2025 · Treatment · Melanoma

    RP1 plus nivolumab after anti-PD-1 failure: IGNYTE and FDA approval

    RP1 is a modified herpes virus injected into tumours and given with nivolumab. In a single-arm trial of people whose melanoma had progressed on anti-PD-1 treatment, about one in three responded in the journal report. The US regulator granted accelerated approval in August 2026.

    IGNYTE: single-arm trial of RP1 plus nivolumab after anti-PD-1 progression (140 enrolled). Journal report: confirmed ORR 32.9% (95% CI 25.2 to 41.3; RECIST 1.1, independent review), 15.0% complete response; median DOR 33.7 months. FDA accelerated approval 6 Aug 2026 on ORR 24.2% (95% CI 15.8 to 34.3) and median DOR 14.1 months in 91 evaluable patients.

  175. 2025 · Treatment · Multiple myeloma

    Bispecifics move earlier: MajesTEC-3, MajesTEC-9, MonumenTAL-3

    Three randomised trials tested bispecific antibodies after only one to three earlier treatments. Teclistamab with daratumumab, teclistamab alone, and talquetamab with daratumumab each lowered the risk of progression or death compared with standard regimens. Serious side effects were more frequent with the teclistamab regimens, including severe infections in the teclistamab-alone trial.

    Randomised phase 3, PFS primary. MajesTEC-3 (teclistamab-daratumumab versus DPd or DVd, n=587): 36-month PFS 83.4% versus 29.7%, HR 0.17 (95% CI 0.12 to 0.23). MajesTEC-9 (teclistamab versus PVd or Kd, n=593): 18-month PFS 69.8% versus 26.9%, HR 0.29 (0.23 to 0.38); OS HR 0.60 (0.43 to 0.83). MonumenTAL-3 (n=864): Tal-DP versus DPd HR 0.28 (0.20 to 0.40); Tal-D versus DPd HR 0.33 (0.24 to 0.46).

  176. 2025 · Treatment · Oesophageal cancer

    ESOPEC: perioperative FLOT versus CROSS in adenocarcinoma

    Two randomised trials compared the two main approaches before surgery for oesophageal adenocarcinoma: chemotherapy before and after surgery, or chemotherapy with radiotherapy before surgery. ESOPEC, using the FLOT regimen, reported longer survival with chemotherapy alone; Neo-AEGIS, mostly using an older regimen, found similar survival but closed early.

    ESOPEC (N=438, resectable oesophageal adenocarcinoma): perioperative FLOT vs preoperative carboplatin-paclitaxel with 41.4 Gy, plus surgery; 3-year OS 57.4% vs 50.7% (HR 0.70; 95% CI 0.53 to 0.92; P=0.01); 3-year PFS 51.6% vs 35.0% (HR 0.66). Neo-AEGIS (362 analysed; closed early, underpowered): perioperative chemotherapy, predominantly a modified MAGIC regimen, vs CROSS-type trimodality therapy; median OS 48.0 vs 49.2 months (HR 1.03; 95% CI 0.77 to 1.38).

  177. 2025 · De-escalation · Oesophageal cancer

    SANO: active surveillance versus surgery after complete response

    In the Dutch SANO trial, people whose oesophageal cancer could no longer be detected after chemotherapy with radiotherapy either had surgery straight away or were closely monitored, with surgery later if needed. Two-year survival with monitoring met the trial's non-inferiority definition, but the authors say longer follow-up is needed.

    SANO (stepped-wedge cluster-randomised non-inferiority phase 3, 12 Dutch hospitals; 309 patients with clinical complete response after neoadjuvant chemoradiotherapy): 2-year OS 74% (95% CI 69 to 78) with active surveillance vs 71% (62 to 78) with standard surgery, modified intention-to-treat (HR 1.14; 95% CI 0.74 to 1.78); intention-to-treat 75% vs 70% (HR 0.83). Median follow-up 38 months.

  178. 2025 · Treatment · Ovarian cancer

    Relacorilant plus nab-paclitaxel, platinum-resistant: ROSELLA

    Relacorilant is a pill that blocks the glucocorticoid receptor; the trial authors say it increases a tumour's sensitivity to chemotherapy. In ROSELLA, adding it to nab-paclitaxel for platinum-resistant ovarian cancer delayed progression by about one month and extended median survival by about four months. All participants had already received bevacizumab.

    ROSELLA (N=381, platinum-resistant, all with prior bevacizumab): relacorilant plus nab-paclitaxel vs nab-paclitaxel alone. Median PFS by blinded central review 6.54 vs 5.52 months, HR 0.70 (95% CI 0.54-0.91), p=0.0076. Final OS 16.0 vs 11.9 months, HR 0.65 (0.51-0.83), p=0.0004; 18-month OS 46% vs 27%.

  179. 2025 · Treatment · Pancreatic cancer

    PANOVA-3: tumour treating fields plus chemotherapy, locally advanced

    In 571 people with newly diagnosed locally advanced pancreatic cancer that could not be removed, adding a wearable electric-field device to chemotherapy lengthened median survival from about 14 to about 16 months. Skin reactions from the device were common. The US regulator approved the device in February 2026.

    PANOVA-3, open-label phase 3: 571 patients with unresectable locally advanced pancreatic adenocarcinoma; TTFields plus gemcitabine/nab-paclitaxel vs chemotherapy alone. Median OS 16.2 (95% CI 15.0-18.0) vs 14.2 months (12.8-15.4); HR 0.82 (0.68-0.99; P=.039). PFS, local PFS and ORR not improved. Device-related skin adverse events 76.3% (grade 3: 7.7%). FDA PMA decision 11 February 2026.

  180. 2025 · Treatment · Pancreatic cancer

    PREOPANC-2: neoadjuvant FOLFIRINOX versus chemoradiotherapy

    PREOPANC-2 compared FOLFIRINOX before surgery with gemcitabine chemoradiotherapy before surgery in resectable or borderline resectable pancreatic cancer. Median survival was 21.9 against 21.3 months, with no clear difference. The authors say both approaches may be considered.

    PREOPANC-2 (Janssen 2025): open-label phase 3, 375 randomised (188 FOLFIRINOX, 187 chemoradiotherapy), 369 in the modified ITT population. FOLFIRINOX x8 then surgery without adjuvant therapy vs gemcitabine plus 36 Gy then surgery and adjuvant gemcitabine. Median OS 21.9 vs 21.3 months, HR 0.88 (95% CI 0.69-1.13), p=0.32. Grade 3 or worse adverse events 67% vs 60% (p=0.20).

  181. 2025 · Treatment · Prostate cancer

    Biomarker-selected mHSPC: AMPLITUDE (BRCA) and CAPItello-281 (PTEN)

    Two phase 3 trials added a targeted drug to abiraterone from the start of hormone therapy in men whose cancer had spread but was still hormone-sensitive and carried a specific tumour change: DNA-repair gene alterations (niraparib) or PTEN loss (capivasertib). Both delayed progression on imaging; survival data were immature. FDA approvals are narrower: BRCA2 mutations and PTEN-deficient tumours.

    AMPLITUDE (phase 3, N=696, HRR-altered mCSPC): niraparib + abiraterone/prednisone vs placebo + same; rPFS HR 0.52 in the BRCA subgroup (95% CI 0.37-0.72) and 0.63 overall (0.49-0.80); OS immature (HR 0.79; 0.59-1.04). CAPItello-281 (phase 3, PTEN-deficient mHSPC, N=1012): capivasertib + abiraterone, rPFS 33.2 vs 25.7 months (HR 0.81; 0.66-0.98); OS HR 0.90 (0.71-1.15; 26.4% maturity).

  182. 2026 · Treatment · Bladder cancer

    KEYNOTE-B15/EV-304: EV-pembrolizumab versus cisplatin-gemcitabine

    In people with muscle-invasive bladder cancer who could receive cisplatin, enfortumab vedotin plus pembrolizumab before and after surgery was compared with cisplatin-gemcitabine chemotherapy before surgery. At two years, 79% were event-free versus 66%, and 87% were alive versus 81%. Severe side effects were more frequent with the new combination. The FDA approved it in July 2026.

    KEYNOTE-B15/EV-304 (phase 3, n=808, cisplatin-eligible MIBC): perioperative EV-pembrolizumab (405) vs neoadjuvant cisplatin-gemcitabine then cystectomy (403). Median time to data cutoff 33.6 months. 2-year EFS 79.4% vs 66.2% (HR 0.53, 95% CI 0.41-0.70); OS 86.9% vs 81.3% (HR 0.65, 0.48-0.89, P=0.006); pCR 55.8% vs 32.5%. Grade 3 or higher adverse events 75.7% vs 67.2%. FDA approval 10 July 2026.

  183. 2026 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

    Blinatumomab replaces chemotherapy cycles in high-risk B-ALL

    In a European trial, 709 children with high-risk B-cell ALL were randomly given two cycles of blinatumomab or two cycles of chemotherapy after consolidation. At a planned interim analysis, about 83 in 100 of the blinatumomab group and 70 in 100 of the chemotherapy group were free of relapse and other events at four years, with fewer infections.

    AIEOP-BFM ALL 2017, phase 3: 709 of 768 eligible patients with high-risk B-ALL randomised after consolidation to two blinatumomab cycles (358) or two chemotherapy cycles (351). Planned interim analysis, median follow-up 2.9 years: 4-year EFS 83.0% (95% CI 77.4-87.4) versus 70.3% (63.8-75.9), HR 0.51 (0.35-0.73), P=0.0002 (ITT). Trial-related infection 23.9% versus 69.4%; neurotoxic events 12.0% versus 3.2%.

  184. 2026 · Treatment · Chronic lymphocytic leukaemia

    BRUIN CLL-322: pirtobrutinib added to venetoclax-rituximab

    In people with previously treated CLL, adding the BTK inhibitor pirtobrutinib to a fixed course of venetoclax plus rituximab left more people free of progression at two years (about 87% versus 72%). Most had taken a covalent BTK inhibitor before. This is an interim analysis of an ongoing trial.

    BRUIN CLL-322 (open-label phase 3; 639 randomised, 321 vs 318): pirtobrutinib-venetoclax-rituximab vs venetoclax-rituximab, IRC-assessed PFS at a prespecified interim analysis (median follow-up 27.3 months): HR 0.547 (95% CI 0.400 to 0.748; P=0.0001); 24-month PFS 87% vs 72%; median PFS not reached vs 39.7 months. 80% had prior covalent BTK inhibitor exposure. Grade 3 or higher adverse events 79% vs 73%.

  185. 2026 · Treatment · Colorectal cancer

    ATOMIC: atezolizumab plus adjuvant FOLFOX in dMMR stage III colon

    In ATOMIC, people with stage III colon cancer with mismatch repair deficiency were randomly given FOLFOX alone or with atezolizumab, an immunotherapy continued for a year. At three years about eighty-six in a hundred were alive without recurrence with atezolizumab, against about seventy-six. Severe side effects were more common with it. The FDA approved the combination on 8 October 2026.

    ATOMIC (Sinicrope 2026): phase 3, 712 patients with resected stage III dMMR colon cancer randomised 1:1 to atezolizumab plus mFOLFOX6 for 6 months then atezolizumab (12 months in total; n=355) or mFOLFOX6 alone (n=357). Median follow-up 40.9 months: 3-year DFS 86.3% (95% CI 81.8-89.8) vs 76.2% (70.9-80.6); HR 0.50 (0.35-0.73), P<0.001. Grade 3-4 adverse events 84.1% vs 71.9%. 5-year OS 89.7% vs 87.9% (HR 0.90, 0.55-1.47), immature.

  186. 2026 · Today · Endometrial cancer

    Where treatment for advanced endometrial cancer stands in 2026

    For people with advanced or recurrent endometrial cancer, first-line treatment in the United States now combines carboplatin and paclitaxel with an immune checkpoint antibody, then continues the antibody alone. Which antibody and which tumours are covered differs by drug. After platinum, mismatch repair status and HER2 status shape the options.

    FDA-labelled first line: dostarlimab or pembrolizumab with carboplatin-paclitaxel for primary advanced or recurrent disease (no biomarker restriction in the labels); durvalumab for dMMR disease only; olaparib has no endometrial indication. After prior systemic therapy: pembrolizumab alone for MSI-H/dMMR, dostarlimab alone for dMMR, pembrolizumab plus lenvatinib for pMMR/not MSI-H, and trastuzumab deruxtecan for HER2 IHC 3+ solid tumours.

  187. 2026 · Treatment · Gastric and gastro-oesophageal junction cancer

    HERIZON-GEA-01: zanidatamab, with or without tislelizumab

    In 2026 a phase 3 trial reported that zanidatamab, an antibody that binds HER2 in two places, added to chemotherapy delayed progression compared with trastuzumab plus chemotherapy in HER2-positive cancers of the stomach, junction and oesophagus. Adding tislelizumab also lengthened survival at this early analysis. US approvals followed in August 2026.

    HERIZON-GEA-01 (open-label phase 3, 1:1:1; median follow-up 25.9 months) vs trastuzumab plus chemotherapy. PFS: median 12.4 months with zanidatamab plus tislelizumab and chemotherapy (HR 0.63, 95% CI 0.51 to 0.78) and 12.4 with zanidatamab plus chemotherapy (HR 0.65, 0.52 to 0.81) vs 8.1 months. OS (interim): 26.4 vs 19.2 months, HR 0.72 (0.57 to 0.90), P=0.004; zanidatamab plus chemotherapy HR 0.80 (0.64 to 1.01).

  188. 2026 · Reversal · Hepatocellular carcinoma

    IMbrave050: early recurrence-free benefit not sustained on update

    A trial gave atezolizumab plus bevacizumab for one year, or active monitoring, to 668 people at high risk of recurrence after liver cancer surgery or ablation. A 2023 interim analysis reported fewer recurrences or deaths with the combination, but a 2026 update found no sustained benefit, and its authors do not support adjuvant use.

    Open-label phase 3, N=668 (334 per arm) after resection or ablation at high risk of recurrence: atezolizumab plus bevacizumab for 17 cycles vs active surveillance. Interim analysis (median follow-up 17.4 months): IRF-assessed RFS HR 0.72 (adjusted 95% CI 0.53-0.98; p=0.012). Updated post hoc analysis: RFS HR 0.90 (95% CI 0.72-1.12); second interim OS HR 1.26 (95% CI 0.85-1.87), immature.

  189. 2026 · Treatment · Kidney cancer (renal cell carcinoma)

    LITESPARK-011: belzutifan plus lenvatinib versus cabozantinib (2026)

    After immunotherapy, people with advanced clear cell kidney cancer received belzutifan plus lenvatinib or cabozantinib. Median time without progression was 14.8 versus 10.7 months in the published analysis. Survival was not significantly different. The FDA approved the combination in September 2026.

    LITESPARK-011 (phase 3, open-label, n=747) after anti-PD-1/PD-L1 therapy: belzutifan 120 mg plus lenvatinib 20 mg vs cabozantinib 60 mg daily. Second interim analysis (median follow-up 29.0 months): median PFS 14.8 vs 10.7 months, HR 0.70 (95% CI 0.59-0.84); OS 34.9 vs 27.6 months, HR 0.85 (0.68-1.05), not significant. FDA page: ORR 53% vs 40%; final OS HR 0.85 (0.70-1.03), not significant. FDA approval 24 September 2026.

  190. 2026 · Treatment · Kidney cancer (renal cell carcinoma)

    LITESPARK-022: adjuvant belzutifan added to pembrolizumab (2026)

    After kidney cancer surgery, everyone received pembrolizumab, and half also took belzutifan tablets for up to a year. At two years, about 81 in 100 on the combination and 74 in 100 on pembrolizumab alone were free of recurrence. Serious side effects were more common with belzutifan. Survival data were still too early to compare.

    Phase 3, double-blind; clear-cell RCC at increased recurrence risk after nephrectomy; pembrolizumab 400 mg every 6 weeks plus belzutifan 120 mg daily (n=921) vs pembrolizumab plus placebo (n=920), up to 1 year. Interim analysis, median 28.4 months: investigator-assessed DFS HR 0.72 (95% CI 0.59-0.87; P<0.001); 24-month DFS 80.7% vs 73.7%. OS HR 0.78 (95% CI 0.51-1.19) with 29% of events; grade 3 or higher adverse events 52.1% vs 30.2%.

  191. 2026 · De-escalation · Multiple myeloma

    ENDURANCE: continuous or fixed-duration lenalidomide

    In people with standard-risk newly diagnosed myeloma who did not have an up-front transplant, lenalidomide maintenance for two years was compared with maintenance until progression. Overall survival at seven years was about 69 percent in both groups. Serious non-blood side effects and second cancers were less frequent with the two-year course.

    ENDURANCE (E1A11), standard-risk newly diagnosed myeloma without up-front ASCT; second randomisation after proteasome inhibitor-lenalidomide induction: indefinite (n=260) versus 2-year (n=256) lenalidomide. Primary endpoint OS: 7-year OS 68.6% versus 69.0% (difference -0.4 points; 95% CI -9.0 to 8.3; P=0.93), median follow-up 86 months. 7-year PFS 36.1% versus 29.7% (difference 6.4 points; 95% CI -2.6 to 15.4). Grade 3 or higher nonhematologic events 48.2% versus 31.5%.

  192. 2026 · Treatment · Ovarian cancer

    KEYNOTE-B96: pembrolizumab plus weekly paclitaxel, PD-L1 CPS 1+

    KEYNOTE-B96 added the immune checkpoint antibody pembrolizumab to weekly paclitaxel for platinum-resistant ovarian cancer. Disease progressed later and survival was longer. Results were reported for everyone and for tumours with a PD-L1 combined positive score of 1 or more; the US approval covers only the latter.

    KEYNOTE-B96 (N=643, double-blind): pembrolizumab plus weekly paclitaxel vs placebo plus paclitaxel. PFS, CPS 1 or higher: 8.3 vs 7.2 months, HR 0.72 (95% CI 0.58-0.89); overall: 8.3 vs 6.4 months, HR 0.70 (0.58-0.84). OS, CPS 1 or higher (interim): 18.2 vs 14.0 months, HR 0.76 (0.61-0.94); overall (final): 17.7 vs 14.0 months, HR 0.82 (0.69-0.97).

  193. 2026 · Treatment · Pancreatic cancer

    Daraxonrasib: RAS(ON) inhibitor extends survival after prior therapy

    In 500 people with spread pancreatic cancer already treated once, the pill daraxonrasib was compared with chemotherapy. Median survival was about 13 months versus about 7 months. The US regulator approved it in August 2026, and a European committee recommended it in October 2026.

    RASolute 302, open-label phase 3: 500 patients with previously treated metastatic PDAC randomised to daraxonrasib (248) or investigator's-choice chemotherapy (252). RAS G12 population: median OS 13.2 vs 6.6 months, HR 0.40; PFS 7.3 vs 3.5 months, HR 0.45 (P<0.001). Overall population OS 13.2 vs 6.7 months, HR 0.40 (95% CI 0.30-0.53; FDA page). Grade 3 or higher adverse events 61.8% vs 69.6%.

  194. 2026 · Treatment · Prostate cancer

    177Lu-PSMA-617 plus ARPI in PSMA-positive mHSPC (PSMAddition)

    In men with PSMA-positive prostate cancer that had spread but was still hormone-sensitive, adding a PSMA-targeted radioactive drug to standard hormone treatment lowered the risk of progression on imaging or death by 28% at the second interim analysis. Survival data were immature. The FDA approved this use on 31 July 2026, before the results were published.

    PSMAddition (phase 3, open-label, N=1144): PSMA-positive metastatic hormone-sensitive disease, 177Lu-PSMA-617 plus ADT and ARPI vs ADT plus ARPI. Second interim analysis (data cutoff 13 January 2025): rPFS by blinded central assessment HR 0.72 (95% CI 0.58-0.90; P=0.0021), median not reached in either arm; 139 (24%) vs 172 (30%) events. Overall survival immature per the FDA.

  195. 2026 · Reversal · Sarcoma and GIST

    Tazemetostat: epithelioid sarcoma accelerated approval withdrawn

    Tazemetostat, a tablet that blocks the EZH2 protein, received US accelerated approval in January 2020 for advanced epithelioid sarcoma after a single-arm study in which 9 of 62 people (15%) responded. In March 2026 the manufacturer withdrew it after a safety signal in a lymphoma trial; the FDA lists the sarcoma approval as withdrawn on 22 June 2026.

    Single-arm phase 2 basket study, epithelioid sarcoma cohort (N=62, INI1/SMARCB1 loss, tazemetostat 800 mg twice daily): objective response 15% (9 of 62; 95% CI 7-26; primary); median PFS 5.5 months; median OS 19.0 months; median follow-up 13.8 months. FDA accelerated approval 23 January 2020. Ipsen withdrew the product 9 March 2026 (safety signal in SYMPHONY-1); FDA table: withdrawal 22 June 2026.

  196. 2026 · Today · Testicular germ cell tumors

    EAU 2026 guideline: current chemotherapy recommendations

    The 2026 European Association of Urology guideline text sets out first-line chemotherapy by IGCCCG group: three cycles of BEP for good-prognosis non-seminoma, four for intermediate prognosis, and for poor prognosis four cycles of BEP with intensification considered after an unfavourable marker decline. For first relapse it lists four cycles of VIP, TIP or GIP.

    EAU Guidelines on Testicular Cancer, 2026 edition (web text read October 2026). Good-risk non-seminoma: BEP x3 standard; EP x4 only with a clear contraindication to bleomycin; omission otherwise not recommended. Intermediate: BEP x4. Poor prognosis: BEP x4; primary high-dose chemotherapy has shown no overall survival benefit in RCTs; dose-dense switch after unfavourable marker decline described. First relapse: four cycles of VIP, TIP or GIP (no RCT compares them); high-dose versus conventional dose is being tested in TIGER.