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Bending the Curve Trial by Trial
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Lung and bronchus (respiratory system)

Lung cancer

How tobacco research, CT screening, targeted therapy and immunotherapy reshaped care for non-small cell and small cell lung cancer.

5-year relative survival · United States, SEER 8 registries

11.74%→31.87%

1975 (observed value; first year in the table) to 2018 (observed value; last observed year in the table). Read these with the caveats under “Then and now”.Source

38 milestones, by decade

  • A 1993 reappraisal in the Annals of Occupational Hygiene by Greenberg and Selikoff states that the 1879 report by Harting and Hesse on the miners of Schneeberg was the first description of occupational lung cancer, and that radon and its decay products were identified as the causal agents only by later discovery. The same abstract says the 1879 authors developed methods for measuring airborne and inhaled dust and made recommendations to improve miners' health. The 1879 report itself was not read: the abstract describes it as not readily accessible.
  • In US registry data on the SEER Cancer Stat Facts page, five-year relative survival for lung and bronchus cancer was 11.74% in 1975 and 31.87% in 2018 (SEER 8 series; the page does not say whether the year is the year of diagnosis), while the age-adjusted US death rate was highest (observed values) at 59.08 per 100,000 in 1993 and was 27.90 per 100,000 in 2024. The page does not say how much of the change is due to detection, smoking trends or treatment, and it does not separate non-small cell from small cell disease.
  • FDA granted accelerated approval to gefitinib on 5 May 2003 for non-small cell lung cancer after platinum-based and docetaxel chemotherapy. On 17 June 2005, after confirmatory trials had not verified clinical benefit (the 2015 FDA summary review reports that ISEL did not show an overall survival improvement, hazard ratio 0.89, p=0.11), FDA requested, and the sponsor agreed, that labelling be restricted. The sponsor asked to withdraw approval on 1 February 2011, and the Federal Register published notice of the voluntary withdrawal on 25 April 2012. On 13 July 2015 FDA approved gefitinib again, as first-line treatment of metastatic non-small cell lung cancer with EGFR exon 19 deletions or exon 21 L858R substitution mutations as detected by an FDA-approved test.

Evidence current to October 2026 · Checked against primary sources to the extent possible

A guided tour of 12 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 38
Treatment type
Setting

The age of rays

  1. 1933 · Treatment · SurgeryOne-stage pneumonectomy for lung cancer (Graham and Singer, 1933)A report dated 28 October 1933, reprinted by JAMA in 1984, describes removing an entire left lung in one operation for a cancer that began in an upper-lobe airway. The reprint's abstract calls it apparently the first case in which a whole lung was removed successfully at one stage.Case report (Graham and Singer), as described in the abstract of the 1984 JAMA reprint of the article dated 28 October 1933. The left lung and many tracheobronchial and mediastinal nodes were removed in one stage for a carcinoma arising in the upper-lobe bronchus, close to the lower-lobe bronchus, so that complete removal required the entire lung. Described as apparently the first successful one-stage removal of an entire lung. Single case; the abstract gives no outcome.

Chemotherapy

  1. 1964 · Understanding · Understanding1964 US Advisory Committee report links cigarettes to lung cancerIn January 1964 the US Surgeon General released the report of a ten-member expert committee that weighed evidence from many studies. It judged cigarette smoking to be causally related to lung cancer in men, with data for women pointing the same way, and found the risk lowered by stopping.Advisory Committee report released 11 January 1964. Using 29 retrospective studies of lung cancer, seven prospective studies and clinical, autopsy and experimental evidence, it judged cigarette smoking causally related to lung cancer in men. Average male cigarette smokers had approximately a 9- to 10-fold risk and heavy smokers at least 20-fold; risk rose with duration and daily number of cigarettes and was diminished by stopping. Data for women were less extensive but pointed the same way.

Molecular origins

  1. 1995 · Understanding · Chemotherapy⚑ needs reviewNSCLC chemotherapy meta-analysis of 52 trials (BMJ 1995)A 1995 analysis pooled individual patient data from 52 randomised trials covering 9,387 people with non-small cell lung cancer. It reported the risk of death as 13 percent lower when chemotherapy was added to surgery or to radical radiotherapy, and 27 percent lower when added to supportive care.NSCLC Collaborative Group, individual patient data meta-analysis: 52 randomised trials, 9387 patients, 7151 deaths. Added chemotherapy: surgery HR 0.87 (absolute benefit 5% at 5 years); radical radiotherapy HR 0.87 (4% at 2 years); supportive care HR 0.73 (10% at 1 year). Modern cisplatin regimens favoured chemotherapy in all comparisons. Older trials with long-term alkylating agents tended to show a detrimental effect of chemotherapy. Confidence intervals not in the abstract.

Targeted therapy

  1. 1999 · Treatment · RadiationProphylactic cranial irradiation in SCLC (1999 and 2007)Prophylactic cranial irradiation (PCI) is brain radiotherapy given before any brain metastases are seen. A 1999 pooled analysis of seven trials in people with small-cell lung cancer in complete remission found better survival with PCI (3-year survival 20.7% vs 15.3%). A 2007 randomised trial in extensive-stage disease found fewer symptomatic brain metastases and longer survival with PCI.Aupérin 1999 (individual-patient-data meta-analysis, 7 trials, N=987, complete remission): relative risk of death 0.84 (95% CI 0.73-0.97; P=0.01); 3-year survival 20.7% vs 15.3%; relative risk of brain metastasis 0.46. Slotman 2007 (randomised, extensive-stage SCLC after chemotherapy response, 143 vs 143): symptomatic brain metastases HR 0.27 (0.16-0.44); 1-year cumulative risk of brain metastases 14.6% vs 40.4%; median OS 6.7 vs 5.4 months. Reported separately, not pooled.
  2. 1999 · Treatment · Radiation⚑ needs reviewLimited-stage SCLC: twice-daily thoracic radiotherapy (Turrisi 1999)In 1999 a randomised trial of 417 people with limited-stage small-cell lung cancer compared chest radiotherapy given twice a day over three weeks with once a day over five weeks, both with cisplatin-etoposide chemotherapy. Median survival was 23 months with twice-daily and 19 with once-daily treatment; severe esophagitis was more common with twice-daily (27% vs 11%).Turrisi 1999 (417 patients, limited-stage SCLC; four cycles of cisplatin-etoposide with 45 Gy thoracic radiotherapy twice daily over 3 weeks vs once daily over 5 weeks): median survival 23 vs 19 months (P=0.04, log-rank); 2-year survival 47% vs 41%, 5-year 26% vs 16%; grade 3 esophagitis 27% vs 11% (P<0.001). CONVERT (547 patients; 45 Gy twice daily vs 66 Gy once daily): median OS 30 vs 25 months (HR 1.18; 0.95-1.45; P=0.14).
  3. 2004 · Treatment · Chemotherapy⚑ needs reviewAdjuvant cisplatin after resection: IALT, JBR.10 and LACEBetween 2004 and 2008, three randomised trials and a pooled analysis of five trials tested cisplatin-based chemotherapy after complete surgery for non-small cell lung cancer. In the first trial, IALT, about 44 in 100 patients on chemotherapy and 40 in 100 on observation were alive at five years. Each trial reported its own population and results.IALT (n=1867, resected stage I-III): 5-year OS 44.5% vs 40.4% (HR 0.86, 95% CI 0.76-0.98). JBR.10 (n=482, stage IB-II, vinorelbine-cisplatin): median OS 94 vs 73 months (HR 0.69, P=0.04). ANITA (n=840, stage IB-IIIA): median OS 65.7 vs 43.7 months (adjusted HR 0.80, 95% CI 0.66-0.96). LACE pooled five trials (n=4584): OS HR 0.89 (95% CI 0.82-0.96); stage IA HR 1.40 (95% CI 0.95-2.06).
  4. 2004 · Understanding · UnderstandingEGFR mutations explain response to gefitinib (2004)In 2004 three research groups reported that lung tumours that shrank on gefitinib, a pill that blocks the EGFR growth-signal receptor, usually carried changes in the EGFR gene, while tumours that did not respond mostly did not. This helped explain why only some people benefited and made testing tumours for EGFR changes a logical next step.Lynch (NEJM): kinase-domain EGFR mutations in 8 of 9 gefitinib-responsive tumours and 0 of 7 non-responders (P<0.001); 2 of 25 untreated tumours (8%). Paez (Science): mutations in 15 of 58 tumours from Japan and 1 of 61 from the United States. Pao (PNAS): 7 of 10 gefitinib-sensitive and 0 of 8 refractory tumours (P=0.004); 7 of 15 never-smoker adenocarcinomas versus 4 of 81 tumours from smokers (P=0.0001).
  5. 2005 · Reversal · TargetedGefitinib: accelerated approval, restriction and EGFR-mutation returnGefitinib was approved in the US in 2003 because tumours responded in heavily pretreated patients. A large placebo-controlled trial, ISEL, did not show a significant survival gain overall, and in 2005 the US label was restricted. The approval was withdrawn in 2012 at AstraZeneca's request. In 2015 gefitinib returned for first-line treatment of EGFR-mutated lung cancer.FDA accelerated approval 5 May 2003 (ORR 10.6% in 142 patients after platinum and docetaxel). ISEL (n=1692, gefitinib or placebo plus best supportive care): median OS 5.6 vs 5.1 months, HR 0.89 (95% CI 0.77-1.02), p=0.087; never-smokers HR 0.67 (0.49-0.92); Asian patients HR 0.66 (0.48-0.91). Labelling restricted 17 June 2005; withdrawal published 25 April 2012; new NDA approved 13 July 2015 for EGFR exon 19 deletions or L858R.
  6. 2009 · Treatment · TargetedIPASS: gefitinib vs chemotherapy, by EGFR mutation (2009)IPASS compared the pill gefitinib with chemotherapy as first treatment in East Asian people with lung adenocarcinoma who had never smoked or had smoked lightly. Overall gefitinib delayed progression more than chemotherapy, and the result depended on the tumour's EGFR gene: it helped people with an EGFR mutation and did worse than chemotherapy in those without.IPASS (gefitinib 609, carboplatin-paclitaxel 608), untreated advanced pulmonary adenocarcinoma, East Asian nonsmokers or former light smokers. 12-month PFS 24.9% vs 6.7%; ITT HR 0.74 (95% CI 0.65-0.85; P<0.001). EGFR-mutation-positive subgroup (n=261): HR 0.48 (0.36-0.64). Mutation-negative subgroup (n=176): HR for progression or death with gefitinib 2.85 (2.05-3.98).
  7. 2010 · Treatment · TargetedCrizotinib for ALK-positive lung cancer (2010-2014)In 2010 a trial of crizotinib, a pill that blocks the ALK protein, reported tumour shrinkage in more than half of 82 people whose lung cancers carried an ALK rearrangement. The US FDA approved it in 2011 on the basis of response rate, and randomised trials later found longer time without progression than with chemotherapy.Kwak 2010 (single-group expanded cohort, n=82 ALK-positive): ORR 57%; estimated 6-month PFS 72%. PROFILE 1007 (n=347, previously treated): median PFS 7.7 vs 3.0 months, HR 0.49 (0.37-0.64). PROFILE 1014 (n=343, untreated nonsquamous): median PFS 10.9 vs 7.0 months (independent review), HR 0.45 (0.35-0.60); OS HR 0.82 (0.54-1.26).
  8. 2010 · Treatment · RadiationSBRT for medically inoperable early-stage lung cancer (RTOG 0236)A North American phase 2 study gave focused, high-dose radiotherapy in three treatments to 55 evaluable patients with early-stage lung cancers under 5 cm who could not have surgery. At three years, an estimated 98 in 100 had no failure of the treated tumour and 56 in 100 were alive. Some patients had serious side effects.RTOG 0236, phase 2: 59 accrued, 55 evaluable (44 T1, 11 T2); medically inoperable peripheral T1-T2N0M0 NSCLC; SBRT 18 Gy x 3 (54 Gy). Median follow-up 34.4 months. At 3 years: primary tumour control 97.6% (95% CI 84.3-99.7), primary tumour and involved lobe 90.6%, local-regional control 87.2%, DFS 48.3%, OS 55.8%; median OS 48.1 months. Grade 3 events 12.7%, grade 4 3.6%, no grade 5. One regimen, no comparison group.

Immunotherapy

  1. 2011 · Detection · Detection & preventionNLST: low-dose CT screening lowers lung-cancer mortalityThe US National Lung Screening Trial gave about 53,000 older people with a heavy smoking history three yearly scans, either low-dose CT or a chest X-ray. Deaths from lung cancer were about one in five lower after CT screening. Many scans were positive, and nearly all of those positive results were false alarms.Randomised trial at 33 US centres: 53,454 people aged 55-74 with at least 30 pack-years were assigned to three annual screens with low-dose CT or chest radiography. Lung-cancer mortality (primary) was 247 vs 309 per 100,000 person-years (CT vs radiography), a 20.0% relative reduction (95% CI 6.8-26.7; P=0.004). All-cause mortality fell 6.7% (95% CI 1.2-13.6; P=0.02). Screens were positive in 24.2% vs 6.9%; 96.4% vs 94.5% of positives were false.
  2. 2014 · Treatment · TargetedROS1-positive NSCLC: crizotinib to taletrectinibROS1 rearrangements define a small group of lung cancers. In 2014 crizotinib shrank tumours in about seven in ten of 50 people in a single-arm cohort. Entrectinib, repotrectinib and taletrectinib followed, each reported in single-arm studies with response rates of roughly three-quarters to nine in ten in people not previously given a ROS1 inhibitor.Single-arm cohorts in ROS1-positive NSCLC. Crizotinib (n=50): ORR 72% (95% CI 58-84), median PFS 19.2 months. Entrectinib integrated analysis (n=53): ORR 77% (64-88), median DOR 24.6 months. Repotrectinib, no previous ROS1 TKI (n=71): ORR 79% (68-88), median PFS 35.7 months; one previous TKI (n=56): ORR 38%, PFS 9.0 months. Taletrectinib pooled, TKI-naive (n=160): ORR 88.8%, median PFS 45.6 months.
  3. 2015 · Treatment · ImmunotherapyPD-(L)1 blockade after chemotherapy: CheckMate, KEYNOTE-010, OAKAfter platinum chemotherapy stopped working, people with advanced lung cancer were randomly given an immune checkpoint inhibitor (nivolumab, pembrolizumab or atezolizumab) or the chemotherapy drug docetaxel. In four trials overall survival was longer with the immune drug, and severe side effects were less common. The FDA approved nivolumab in March 2015, before the first of these trials was published.Four randomised, open-label trials versus docetaxel after platinum-based chemotherapy. CheckMate 017 (squamous, N=272): median OS 9.2 vs 6.0 months (HR 0.59). CheckMate 057 (non-squamous, N=582): 12.2 vs 9.4 months (HR 0.73). KEYNOTE-010 (PD-L1 on at least 1% of tumour cells, N=1034): 10.4 and 12.7 vs 8.5 months. OAK (850 in the primary ITT analysis; 1225 enrolled): 13.8 vs 9.6 months (HR 0.73). Populations and PD-L1 rules differ.
  4. 2016 · Treatment · ImmunotherapyKEYNOTE-024: first-line pembrolizumab for PD-L1 >= 50%In people with advanced lung cancer whose tumours had high levels of the PD-L1 protein and no EGFR or ALK changes, pembrolizumab alone was compared with platinum chemotherapy as first treatment. Cancer took longer to grow and survival was longer with pembrolizumab, which also caused fewer serious side effects. A later analysis kept the survival difference despite crossover.Open-label phase 3; previously untreated advanced NSCLC, PD-L1 on at least 50% of tumour cells, no EGFR/ALK alteration (N=305; 154 vs 151): pembrolizumab 200 mg every 3 weeks vs platinum-based chemotherapy. Median PFS 10.3 vs 6.0 months (HR 0.50; 95% CI 0.37-0.68). Updated median OS 30.0 vs 14.2 months (HR 0.63; 95% CI 0.47-0.86); 82 patients crossed over.
  5. 2016 · Treatment · ImmunotherapyPembrolizumab plus chemotherapy first-line: KEYNOTE-021G, -189, -407Adding pembrolizumab to platinum chemotherapy was tested as first treatment for advanced lung cancer without EGFR or ALK changes, in non-squamous disease (KEYNOTE-189) and squamous disease (KEYNOTE-407). In both trials people lived longer and the cancer took longer to grow than with chemotherapy plus placebo. Each trial answers its own question and they are not compared.Two double-blind phase 3 trials of platinum chemotherapy plus pembrolizumab or placebo. Non-squamous, no EGFR/ALK alteration (KEYNOTE-189; N=616, 2:1): 12-month OS 69.2% vs 49.4% (HR 0.49; 95% CI 0.38-0.64); updated median OS 22.0 vs 10.7 months (HR 0.56). Squamous (KEYNOTE-407; N=559, 1:1): median OS 15.9 vs 11.3 months (HR 0.64; 95% CI 0.49-0.85).
  6. 2017 · Treatment · ImmunotherapyPACIFIC: durvalumab after chemoradiotherapy, stage IIIFor people with stage III lung cancer that surgery could not remove and that had not grown after chemotherapy with radiation, a year of the immune drug durvalumab was compared with placebo. Cancer took longer to grow with durvalumab, and later reports showed longer survival. More people stopped durvalumab because of side effects.Phase 3, randomised 2:1, placebo-controlled; unresectable stage III NSCLC without progression after chemoradiotherapy (N=713): durvalumab 10 mg per kilogram every 2 weeks for up to 12 months. Median PFS 16.8 vs 5.6 months (HR 0.52; 95% CI 0.42-0.65). OS at 24 months 66.3% vs 55.6% (HR 0.68). Exploratory 5-year update: median OS 47.5 vs 29.1 months (HR 0.72).
  7. 2017 · Treatment · TargetedALEX: alectinib vs crizotinib first-lineIn ALEX, people with untreated ALK-positive lung cancer were randomly given alectinib or crizotinib. Alectinib kept the cancer from progressing for a median of 34.8 months in the later analysis, against 10.9 months with crizotinib, and brain progression was much less frequent. A final analysis of survival followed in 2025.ALEX (N=303; alectinib 152, crizotinib 151), untreated ALK-positive advanced NSCLC. Primary analysis: 12-month event-free rate 68.4% vs 48.7%, HR 0.47 (0.34-0.65). Mature investigator-assessed PFS: median 34.8 vs 10.9 months, HR 0.43 (0.32-0.58). Final OS: median 81.1 vs 54.2 months, HR 0.78 (0.56-1.08), interval including 1.
  8. 2017 · Treatment · TargetedFLAURA: osimertinib versus gefitinib or erlotinib, first lineIn people with untreated advanced lung cancer carrying an EGFR change, the pill osimertinib kept the cancer from growing for a median of about nineteen months, against about ten months with the older pills gefitinib or erlotinib. A later analysis also found longer survival with osimertinib.FLAURA (N=556), untreated EGFR exon 19 deletion/L858R advanced NSCLC, double-blind: osimertinib vs gefitinib or erlotinib. Investigator-assessed median PFS 18.9 vs 10.2 months, HR 0.46 (95% CI 0.37-0.57; P<0.001). Final OS: median 38.6 vs 31.8 months, HR 0.80 (95.05% CI 0.64-1.00; P=0.046). Grade 3 or higher adverse events 34% vs 45% at the primary analysis.
  9. 2018 · Treatment · ImmunotherapyExtensive-stage SCLC: chemotherapy plus atezolizumab or durvalumabTwo randomised trials added an immune checkpoint inhibitor, atezolizumab or durvalumab, to platinum-etoposide chemotherapy for newly diagnosed extensive-stage small-cell lung cancer. Typical survival was about two to three months longer with the added drug: around 12 months versus 10 in one trial, and 13 versus 10 in the other. The trials were run separately and are not compared.IMpower133 (double-blind; atezolizumab 201 vs placebo 202, each with carboplatin-etoposide): median OS 12.3 vs 10.3 months (HR 0.70; 95% CI 0.54-0.91; P=0.007); median PFS 5.2 vs 4.3 months. CASPIAN (open-label; durvalumab plus platinum-etoposide vs platinum-etoposide, planned interim analysis): median OS 13.0 vs 10.3 months (HR 0.73; 0.59-0.91; P=0.0047); 18-month OS 34% vs 25%. Separate trials; not directly comparable.

Precision & engineered

  1. 2020 · Treatment · TargetedCROWN: lorlatinib first-line, long follow-upCROWN 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.
  2. 2020 · Treatment · ChemotherapyLurbinectedin in SCLC: 2020 approval, IMforte, 2026 withdrawalLurbinectedin 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.
  3. 2020 · Detection · Detection & prevention⚑ needs reviewNELSON: volume-CT screening and lung-cancer mortalityThe 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%.
  4. 2020 · Treatment · TargetedMET exon 14 skipping: capmatinib and tepotinibAbout 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).
  5. 2020 · Treatment · TargetedRET fusion-positive NSCLC: selpercatinib and pralsetinibRET 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.
  6. 2020 · Treatment · TargetedADAURA: adjuvant osimertinib after resectionAfter 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).
  7. 2021 · Treatment · Immunotherapy⚑ needs reviewAdjuvant PD-(L)1 after resection: IMpower010 and PEARLSAfter 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.
  8. 2021 · Treatment · Antibody–drug conjugateHER2-mutant NSCLC: trastuzumab deruxtecan and oral TKIsSome 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).
  9. 2021 · Treatment · ImmunotherapyEGFR exon 20 insertions: amivantamab, CHRYSALIS to PAPILLONEGFR 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.
  10. 2021 · Treatment · TargetedKRAS G12C inhibitors: sotorasib and adagrasibKRAS 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.
  11. 2022 · Treatment · ImmunotherapyCheckMate 816: neoadjuvant nivolumab plus chemotherapyBefore 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%.
  12. 2022 · De-escalation · SurgerySegmentectomy 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.
  13. 2023 · Treatment · ImmunotherapyPerioperative chemo-immunotherapy: KEYNOTE-671, AEGEAN, CheckMate 77TThree 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).
  14. 2023 · Treatment · ImmunotherapyTarlatamab: DLL3 T-cell engager for previously treated SCLCTarlatamab 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.
  15. 2023 · Treatment · TargetedFirst-line EGFR combinations: FLAURA2 and MARIPOSATwo 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).
  16. 2024 · Treatment · ImmunotherapyADRIATIC: durvalumab after chemoradiotherapy, limited-stage SCLCSome 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.
  17. 2024 · Treatment · TargetedALINA: adjuvant alectinib in resected ALK-positive diseaseAfter 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.
  18. 2024 · Treatment · TargetedLAURA: osimertinib after chemoradiotherapy, stage IIIIn 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%.

Then and now

  • 5-year relative survival · United States, SEER 8 registries

    • 11.74%

      1975 (observed value; first year in the table)

    All races, both sexes; lung and bronchus cancer (non-small cell and small cell lung cancer are not reported separately on the page); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts lung and bronchus page. Age range is not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column. The page headings and chart note ('SEER 8 5-Year Relative Survival Percent from 1975-2018') do not label the 'Year' column as year of diagnosis. SEER 8 covers a limited set of registries. Changes over time in how lung cancer is found, staged and classified (for example screening with low-dose CT: the USPSTF 2021 statement replaces a 2013 statement that already recommended annual low-dose CT for a defined high-risk group) can raise survival measured from diagnosis through earlier detection and case-mix change as well as through treatment; the SEER page does not describe such changes, does not apportion the rise and attributes it to no cause. Read beside the mortality values. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 15.51%

      2000 (observed value)

    All races, both sexes; lung and bronchus cancer (non-small cell and small cell lung cancer are not reported separately on the page); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts lung and bronchus page. Age range is not stated for this series.

    Observed single-year value (modelled trend for 2000: 15.22%). Included because the series stays between 11.74% and 15.96% in every observed year from 1975 to 2003 and rises mainly after 2003, so the whole change did not occur evenly across the period. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column. The page headings and chart note ('SEER 8 5-Year Relative Survival Percent from 1975-2018') do not label the 'Year' column as year of diagnosis. SEER 8 covers a limited set of registries. Changes over time in how lung cancer is found, staged and classified (for example screening with low-dose CT: the USPSTF 2021 statement replaces a 2013 statement that already recommended annual low-dose CT for a defined high-risk group) can raise survival measured from diagnosis through earlier detection and case-mix change as well as through treatment; the SEER page does not describe such changes, does not apportion the rise and attributes it to no cause. Read beside the mortality values. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 31.87%

      2018 (observed value; last observed year in the table)

    All races, both sexes; lung and bronchus cancer (non-small cell and small cell lung cancer are not reported separately on the page); SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts lung and bronchus page. Age range is not stated for this series.

    Observed single-year value (modelled trend for 2018: 31.38%). Entries for 2019-2023 in the table are modelled trend values only (32.41% to 36.55%) and are not used. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modelled trend value in the adjacent column. The page headings and chart note ('SEER 8 5-Year Relative Survival Percent from 1975-2018') do not label the 'Year' column as year of diagnosis. SEER 8 covers a limited set of registries. Changes over time in how lung cancer is found, staged and classified (for example screening with low-dose CT: the USPSTF 2021 statement replaces a 2013 statement that already recommended annual low-dose CT for a defined high-risk group) can raise survival measured from diagnosis through earlier detection and case-mix change as well as through treatment; the SEER page does not describe such changes, does not apportion the rise and attributes it to no cause. Read beside the mortality values. Compare only with other values from the same SEER 8 series.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 29.5%

      2016-2022

    All races, both sexes; the headline figure on the SEER Cancer Stat Facts lung and bronchus page (SEER 21, excluding IL). Age range is not stated beside the figure. Non-small cell and small cell lung cancer are not reported separately.

    A different registry set and a multi-year period from the SEER 8 series above, so it is not a continuation of that series and must not be subtracted from it. The page labels the period '2016-2022' and does not say whether it is year of diagnosis. Relative survival; the page does not discuss lead-time bias or overdiagnosis.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 65.5%

      2016-2022; localized stage at diagnosis (24% of cases)

    All races, both sexes; lung and bronchus; localized (confined to primary site) by SEER Combined Summary Stage.

    Stage-specific value from the same SEER 21 table as the 29.5% figure. The page states that stage at diagnosis has a strong influence on the length of survival and gives the stage mix as 24% localized, 21% regional, 51% distant and 4% unstaged. It is a five-year figure. Not comparable with SEER 8 values. Stage-specific values for non-small cell and small cell disease separately are not on the page.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 10.5%

      2016-2022; distant stage at diagnosis (51% of cases)

    All races, both sexes; lung and bronchus; distant (cancer has metastasized) by SEER Combined Summary Stage.

    Same SEER 21 table as the 29.5% figure; stage at diagnosis, not histology or molecular subtype, is the only split shown. Not comparable with SEER 8 values.

    Source

  • Age-standardised mortality · United States

    • 42.51per 100,000

      1975 (observed value; first year in the table)

    All races, both sexes; lung and bronchus cancer; age-adjusted death rate from US mortality data (the 'Death Rate - U.S.' column; the page states that deaths come from U.S. Mortality, not SEER registries).

    Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not affected by lead time or overdiagnosis in the way survival from diagnosis can be; they are shown beside survival for that reason. The age-standard population and cause-of-death coding over five decades are not described on the page, and non-small cell and small cell lung cancer are not separated. The page attributes no change to any cause.

    Source

  • Age-standardised mortality · United States

    • 59.08per 100,000

      1993 (observed; highest value in the 1975-2024 table)

    All races, both sexes; lung and bronchus cancer; age-adjusted death rate from US mortality data.

    Highest value in the observed column; neighbouring observed values are 58.95 (1991), 58.85 (1992) and 58.49 (1994). The modelled-trend column peaks at 59.09 in 1990. Same caveats as the 1975 value.

    Source

  • Age-standardised mortality · United States

    • 27.9per 100,000

      2024 (observed)

    All races, both sexes; lung and bronchus cancer; age-adjusted death rate from US mortality data.

    The page headline gives 30.2 per 100,000 for 2020-2024 deaths; use one or the other, not both. The page describes a fall of 4.1% a year on average over 2015-2024 and does not attribute it to smoking trends, screening or treatment. Same caveats as the 1975 value.

    Source

  • 10-year relative survival · United Kingdom

    • 11.1%

      2018 (as labelled on the page; described as predicted)

    People diagnosed with lung cancer in the UK; the CRUK page states that around 1 in 10 (11.1%) are predicted to survive ten years or more (2018). Age range and net versus relative survival are not stated beside the figure.

    Described on the page as predicted, so it is a modelled estimate rather than an observed ten-year follow-up; the page does not name the measure (net, relative or observed survival), and the metric label is the nearest available. The same page gives a 1970s comparator (3.3%) whose accompanying words ('almost 5 in 100') do not match the number, so that value is not used. Not comparable with the US SEER series. Non-small cell and small cell lung cancer are not separated.

    Source

Survival figures are affected by earlier detection (lead time) and overdiagnosis, and by changes in who is diagnosed. For screened cancers, read them alongside mortality.

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

EGFR-mutated metastatic NSCLC, first line

Previously untreated advanced NSCLC with an EGFR mutation · Metastatic · endpoint: PFS

Results are not comparable across trials.

Eras, comparators and review methods differ. FLAURA compared osimertinib with gefitinib or erlotinib (investigator-assessed PFS). FLAURA2 and MARIPOSA each compared a combination with osimertinib alone, so osimertinib is the control arm in both and the two trials were not randomised against each other; FLAURA2's median is from the FDA label (investigator assessment) and MARIPOSA's is by blinded independent central review. IPASS (2009) enrolled East Asian never or light smokers regardless of EGFR status and compared gefitinib with chemotherapy; its mutation-positive PFS is reported as a hazard ratio only, so it is part of the lane's history but is not drawn. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

051015202530PFS, median (months)201720232023FLAURAFLAURA2MARIPOSA
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 3 trials in this lane. FLAURA (2017): experimental 18.9 months vs control 10.2 months; FLAURA2 (2023): experimental 25.5 months vs control 16.7 months; MARIPOSA (2023): experimental 23.7 months vs control 16.6 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
FLAURA2017PFS10.2 months18.9 months
FLAURA22023PFS16.7 months25.5 months
MARIPOSA2023PFS16.6 months23.7 months

ALK-positive metastatic NSCLC, first line

Previously untreated advanced ALK-positive NSCLC · Metastatic · endpoint: PFS

Results are not comparable across trials.

PROFILE 1014 compared crizotinib with pemetrexed-platinum chemotherapy in nonsquamous disease (independent radiologic review). ALEX and CROWN both used crizotinib as the control but were separate trials with different review methods (ALEX investigator-assessed, CROWN blinded independent central review) and follow-up, and they were not compared with each other. Median PFS with lorlatinib was not reached in the CROWN reports, so that result is listed but not drawn on the median axis; it is given as landmark rates and a hazard ratio. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

010203040PFS, median (months)20102017PROFILE 1014ALEX
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 2 trials in this lane. PROFILE 1014 (2010): experimental 10.9 months vs control 7 months; ALEX (2017): experimental 34.8 months vs control 10.9 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
PROFILE 10142010PFS7 months10.9 months
ALEX2017PFS10.9 months34.8 months

Immunotherapy-based first line, no EGFR or ALK alteration

Previously untreated metastatic NSCLC without a sensitising EGFR mutation or ALK alteration · Metastatic · endpoint: OS

Results are not comparable across trials.

The populations differ. KEYNOTE-024 enrolled patients of any histology whose tumours had PD-L1 on at least 50% of cells and compared pembrolizumab alone with platinum chemotherapy, with crossover to pembrolizumab allowed. KEYNOTE-189 enrolled nonsquamous disease at any PD-L1 level and added pembrolizumab to pemetrexed and platinum. Both results are updated analyses, and KEYNOTE-189's update had no alpha assigned. KEYNOTE-407 (squamous disease) belongs to the same milestone but is a different population and is not drawn here. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

05101520253035OS, median (months)20162016KEYNOTE-024KEYNOTE-189
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 2 trials in this lane. KEYNOTE-024 (2016): experimental 30 months vs control 14.2 months; KEYNOTE-189 (2016): experimental 22 months vs control 10.7 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
KEYNOTE-0242016OS14.2 months30 months
KEYNOTE-1892016OS10.7 months22 months

Unresectable stage III NSCLC after chemoradiotherapy

Unresectable stage III NSCLC without progression after concurrent platinum-based chemoradiotherapy · Locally advanced · endpoint: PFS

Results are not comparable across trials.

Both trials compared a drug started after chemoradiotherapy with placebo, but the populations differ. PACIFIC enrolled patients after concurrent chemoradiotherapy regardless of PD-L1 status (durvalumab for up to 12 months); LAURA enrolled only EGFR-mutated disease and allowed concurrent or sequential chemoradiotherapy (osimertinib until progression). Both PFS results are by blinded independent central review, but era, staging methods and follow-up differ. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

010203040PFS, median (months)20172024PACIFICLAURA
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 2 trials in this lane. PACIFIC (2017): experimental 16.8 months vs control 5.6 months; LAURA (2024): experimental 39.1 months vs control 5.6 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
PACIFIC2017PFS5.6 months16.8 months
LAURA2024PFS5.6 months39.1 months

Resectable NSCLC, perioperative chemotherapy plus immunotherapy

Resectable stage II to III NSCLC given platinum chemotherapy with an immune checkpoint inhibitor or placebo before surgery, then the same drug or placebo after · Perioperative · endpoint: EFS

Results are not comparable across trials.

The three trials differ in stage range, drug, EFS definition and analysis timing. KEYNOTE-671's median EFS is from its second interim analysis, whereas AEGEAN (modified ITT, EGFR- or ALK-altered disease excluded) and CheckMate 77T report landmark EFS rates, so those two are listed but not drawn on the median axis. CheckMate 816, which gave nivolumab only before surgery, is a separate neoadjuvant milestone and is not part of this lane. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

01020304050EFS, median (months)2023KEYNOTE-671
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS, median, across 1 trial in this lane. KEYNOTE-671 (2023): experimental 47.2 months vs control 18.3 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
KEYNOTE-6712023EFS18.3 months47.2 months
AEGEAN2023EFS (not plotted: different measure or time point)64.5 %73.4 %
CheckMate 77T2023EFS (not plotted: different measure or time point)50 %70.2 %

Extensive-stage SCLC, first line

Previously untreated extensive-stage small-cell lung cancer · Metastatic · endpoint: OS

Results are not comparable across trials.

IMpower133 added atezolizumab to carboplatin-etoposide and continued it as maintenance, with a placebo control. CASPIAN added durvalumab to platinum-etoposide (carboplatin or cisplatin) against platinum-etoposide alone; its durvalumab-plus-tremelimumab arm is not drawn. CASPIAN's figure is from the updated analysis, IMpower133's from the primary report. IMforte, which randomised patients after induction treatment, is a different population and is not part of this lane. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

02468101214OS, median (months)20182018IMpower133CASPIAN
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 2 trials in this lane. IMpower133 (2018): experimental 12.3 months vs control 10.3 months; CASPIAN (2018): experimental 12.9 months vs control 10.5 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
IMpower1332018OS10.3 months12.3 months
CASPIAN2018OS10.5 months12.9 months

Limited-stage SCLC, thoracic radiotherapy schedule

Limited-stage small-cell lung cancer treated with cisplatin-etoposide and concurrent thoracic radiotherapy · Locally advanced · endpoint: OS

Results are not comparable across trials.

The two trials ask the same question from opposite directions, so the arm roles are reversed. In the 1999 trial twice-daily radiotherapy (45 Gy) is the experimental arm and once-daily the control; in CONVERT (2017) once-daily 66 Gy is the experimental arm and twice-daily 45 Gy the control. The 1999 abstract does not state which arm was the control, so that assignment is a reading of how the abstract frames the comparison. Doses, chemotherapy timing and follow-up differ, and CONVERT did not show a significant difference. Consolidation durvalumab after chemoradiotherapy (ADRIATIC) is a different setting and is not part of this lane. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

05101520253035OS, median (months)19991999turrisi-1999-twice-daily-rtCONVERT
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 2 trials in this lane. turrisi-1999-twice-daily-rt (1999): experimental 23 months vs control 19 months; CONVERT (1999): experimental 25 months vs control 30 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
turrisi-1999-twice-daily-rt1999OS19 months23 months
CONVERT1999OS30 months25 months

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

EGFR-mutated metastatic NSCLC: first-line treatment

Previously untreated advanced NSCLC with an EGFR mutation · Metastatic

  1. Targeted11st line: osimertinib ± chemotherapyFirst-line EGFR combinations: FLAURA2 and MARIPOSA (2023)
  2. Immunotherapy21st line: amivantamab + lazertinibFirst-line EGFR combinations: FLAURA2 and MARIPOSA (2023)
Today. Based only on the trials cited in each step. FLAURA2 and MARIPOSA each tested a combination against osimertinib alone; they were not compared with each other.
Text version
  • 2009: 1st line: gefitinib if EGFR-mutated
  • 2018: 1st line: osimertinib
  • Today: 1st line: osimertinib ± chemotherapy → 1st line: amivantamab + lazertinib

ALK-positive metastatic NSCLC: first-line treatment

Previously untreated advanced ALK-positive NSCLC · Metastatic

  1. Targeted11st line: alectinibALEX: alectinib vs crizotinib first-line (2017)
  2. Targeted21st line: lorlatinibCROWN: lorlatinib first-line, long follow-up (2020)
Today. Based only on the trials cited in each step. Alectinib and lorlatinib were each compared with crizotinib in separate trials, not with each other.
Text version
  • 2014: 1st line: crizotinib
  • 2017: 1st line: alectinib
  • Today: 1st line: alectinib → 1st line: lorlatinib

Reversals and dead ends

Approaches that were abandoned or withdrawn, and trials whose results were later questioned, are part of the story.

  • 2005

    Gefitinib: accelerated approval, restriction and EGFR-mutation return

    Gefitinib was approved in the US in 2003 because tumours responded in heavily pretreated patients. A large placebo-controlled trial, ISEL, did not show a significant survival gain overall, and in 2005 the US label was restricted. The approval was withdrawn in 2012 at AstraZeneca's request. In 2015 gefitinib returned for first-line treatment of EGFR-mutated lung cancer.

    FDA accelerated approval 5 May 2003 (ORR 10.6% in 142 patients after platinum and docetaxel). ISEL (n=1692, gefitinib or placebo plus best supportive care): median OS 5.6 vs 5.1 months, HR 0.89 (95% CI 0.77-1.02), p=0.087; never-smokers HR 0.67 (0.49-0.92); Asian patients HR 0.66 (0.48-0.91). Labelling restricted 17 June 2005; withdrawal published 25 April 2012; new NDA approved 13 July 2015 for EGFR exon 19 deletions or L858R.

Today and tomorrow

Standard of care today

Screening
United States guidelines (abstracts read). The USPSTF recommendation statement (JAMA 2021) recommends annual low-dose CT screening for adults aged 50 to 80 years with a 20 pack-year smoking history who currently smoke or quit within the past 15 years (B recommendation), and states that screening should stop once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have "curative lung surgery" (the statement's wording); it replaces the 2013 statement (ages 55 to 80 years, 30 pack-years). The American Cancer Society 2023 guideline update (CA Cancer J Clin 2024) recommends annual low-dose CT for asymptomatic people aged 50 to 80 years who currently smoke or formerly smoked with a 20 pack-year or greater history (strong recommendation, moderate-quality evidence), after a shared decision-making discussion, and states that years since quitting is not an eligibility criterion to start or stop screening. Only the abstracts were read, and programmes in other countries are not summarised.
Guideline: Krist AH, Davidson KW, Mangione CM, Barry MJ, Cabana M, Caughey AB, et al 2021Guideline: Wolf AMD, Oeffinger KC, Shih TY, Walter LC, Church TR, Fontham ETH, et al 2024
Neoadjuvant
Resectable non-small cell lung cancer, FDA regulatory action read: nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment of adults with resectable (tumors 4 cm or larger, or node positive) disease (4 March 2022). Guideline documents on this topic are cited by reference only, with no recommendation summarised here. Guideline documents: ESMO early and locally advanced NSCLC Clinical Practice Guideline (Zer et al., Ann Oncol 2025) and NCCN NSCLC Version 9.2026 (landing-page title only).
FDA 2022Guideline: Zer A, Ahn MJ, Barlesi F, Bubendorf L, De Ruysscher D, Garrido P, et al 2025Guideline: National Comprehensive Cancer Network 2026
Perioperative

Resectable non-small cell lung cancer, FDA regulatory actions read, each for neoadjuvant treatment with platinum-containing chemotherapy followed by single-agent treatment after surgery:

  • pembrolizumab for resectable (tumors 4 cm or larger, or node positive) disease (16 October 2023)
  • durvalumab for resectable (tumors 4 cm or larger and/or node positive) disease with no known EGFR mutations or ALK rearrangements (15 August 2024)
  • nivolumab with platinum-doublet chemotherapy for resectable (tumors 4 cm or larger, or node positive) disease with no known EGFR mutations or ALK rearrangements (3 October 2024). Guideline documents on this topic are cited by reference only, with no recommendation summarised here
FDA 2023FDA 2024FDA 2024Guideline: Zer A, Ahn MJ, Barlesi F, Bubendorf L, De Ruysscher D, Garrido P, et al 2025Guideline: National Comprehensive Cancer Network 2026
Adjuvant

Resected non-small cell lung cancer, FDA regulatory actions read:

  • osimertinib as adjuvant therapy after tumor resection for EGFR exon 19 deletions or exon 21 L858R mutations (18 December 2020)
  • atezolizumab as a single agent after resection and platinum-based chemotherapy for stage II to IIIA disease with PD-L1 expression on 1% or more of tumor cells (effective action date 15 October 2021, per a corrected letter signed 20 October 2021)
  • pembrolizumab as a single agent after resection and platinum-based chemotherapy for stage IB (T2a, 4 cm or larger), II or IIIA disease (26 January 2023)
  • alectinib as adjuvant treatment after resection of ALK-positive disease with tumors 4 cm or larger or node positive (18 April 2024). Guideline documents on this topic are cited by reference only, with no recommendation summarised here
US Food and Drug Administration 2020FDA 2021FDA 2023US Food and Drug Administration 2024Guideline: Zer A, Ahn MJ, Barlesi F, Bubendorf L, De Ruysscher D, Garrido P, et al 2025Guideline: National Comprehensive Cancer Network 2026
Locally advanced
Unresectable stage III non-small cell lung cancer, FDA regulatory actions read: durvalumab for disease that has not progressed after concurrent platinum-based chemotherapy and radiation therapy (16 February 2018); osimertinib for locally advanced, unresectable (stage III) disease with EGFR exon 19 deletions or exon 21 L858R mutations that has not progressed during or after concurrent or sequential platinum-based chemoradiation (25 September 2024). Guideline documents: ASCO stage III rapid recommendation update (Daly et al., J Clin Oncol 2024, identifier only), ESMO early and locally advanced NSCLC (Zer et al., 2025) and NCCN NSCLC Version 9.2026. Guideline documents on this topic are cited by reference only, with no recommendation summarised here.
FDA 2018US Food and Drug Administration 2024Guideline: Daly ME, Singh N, Ismaila N 2024Guideline: Zer A, Ahn MJ, Barlesi F, Bubendorf L, De Ruysscher D, Garrido P, et al 2025Guideline: National Comprehensive Cancer Network 2026
Locally advanced
Limited-stage small cell lung cancer, FDA regulatory action read: durvalumab as a single agent for disease that has not progressed after concurrent platinum-based chemotherapy and radiation therapy (4 December 2024). Guideline documents: NCCN SCLC Version 1.2027 (landing-page title only), ESMO small-cell lung cancer Clinical Practice Guideline (Dingemans et al., Ann Oncol 2021) and the ASCO systemic therapy rapid recommendation update (Kalemkerian et al., J Clin Oncol 2025; abstract read, which carries no recommendation text). No later ESMO small-cell guideline was found in PubMed. Guideline documents on this topic are cited by reference only, with no recommendation summarised here.
FDA 2024Guideline: National Comprehensive Cancer Network 2026Guideline: Dingemans AC, Früh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks LE, et al 2021Guideline: Kalemkerian GP, Khurshid H, Ismaila N 2025
Metastatic

Non-small cell lung cancer with common EGFR mutations (exon 19 deletions or exon 21 L858R), FDA regulatory actions read:

  • gefitinib as first-line treatment of metastatic disease (13 July 2015)
  • osimertinib for first-line metastatic disease (18 April 2018)
  • osimertinib with pemetrexed and platinum-based chemotherapy for first-line locally advanced or metastatic disease (16 February 2024)
  • amivantamab with lazertinib for first-line locally advanced or metastatic disease (19 August 2024). Later labelling supplements added updated or final overall survival data from the MARIPOSA trial (amivantamab, 14 August 2025) and the FLAURA2 trial (osimertinib, 14 September 2026)
  • these supplements are not new indications. Guideline documents on this topic are cited by reference only, with no recommendation summarised here. Guideline documents: ESMO oncogene-addicted metastatic NSCLC (Hendriks et al., Ann Oncol 2023), ASCO living guideline for stage IV disease with driver alterations (Version 2026.3.3) and NCCN NSCLC Version 9.2026
US Food and Drug Administration 2015US Food and Drug Administration 2018US Food and Drug Administration 2024US Food and Drug Administration 2024US Food and Drug Administration 2025US Food and Drug Administration 2026Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Wheatley-Price P, Ismaila N, Calles Blanco A, Cetnar J, Conneran T, Desai PA, et al 2026Guideline: National Comprehensive Cancer Network 2026
Metastatic

EGFR exon 20 insertion and other EGFR-directed approvals, FDA actions read:

  • amivantamab received accelerated approval for exon 20 insertion disease after platinum-based chemotherapy (21 May 2021)
  • on 1 March 2024 a supplement letter approved amivantamab with carboplatin and pemetrexed as first-line treatment and described the revisions as supporting traditional approval of single-agent amivantamab in the previously treated setting. FDA's withdrawn-approvals list shows that the accelerated approval of mobocertinib for exon 20 insertion disease (15 September 2021) was withdrawn on 15 July 2024. FDA's ongoing accelerated-approvals list (current as of 19 October 2026) includes sunvozertinib for exon 20 insertion disease (2 July 2025) and datopotamab deruxtecan for EGFR-mutated disease after EGFR-directed therapy and platinum-based chemotherapy (23 June 2025)
  • neither letter was opened
US Food and Drug Administration 2021US Food and Drug Administration 2024FDA 2026FDA 2026Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Wheatley-Price P, Ismaila N, Calles Blanco A, Cetnar J, Conneran T, Desai PA, et al 2026
Metastatic

ALK-positive and ROS1-positive non-small cell lung cancer, FDA regulatory actions read. ALK:

  • crizotinib received accelerated approval on 26 August 2011 (FDA's verified list shows the benefit verified on 20 November 2013)
  • a supplement letter of 6 November 2017 expanded alectinib by removing the restriction to patients who had progressed on or were intolerant to crizotinib
  • lorlatinib received accelerated approval on 2 November 2018 for disease that had progressed on specified prior ALK inhibitors and, on 3 March 2021, the restriction and accelerated-approval statements were removed and the indication expanded to ALK-positive metastatic disease. Updated overall survival data from the ALEX trial were added to the alectinib label on 11 June 2026. ROS1: crizotinib (11 March 2016), entrectinib (15 August 2019), repotrectinib (15 November 2023) and taletrectinib (11 June 2025). Guideline documents on this topic are cited by reference only, with no recommendation summarised here. Guideline documents: ESMO oncogene-addicted metastatic NSCLC (Hendriks et al., 2023), ASCO living guideline Version 2026.3.3 and NCCN NSCLC Version 9.2026
US Food and Drug Administration 2011US Food and Drug Administration 2017US Food and Drug Administration 2018US Food and Drug Administration 2021US Food and Drug Administration 2026US Food and Drug Administration 2016US Food and Drug Administration 2019US Food and Drug Administration 2023US Food and Drug Administration 2025FDA 2026Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Wheatley-Price P, Ismaila N, Calles Blanco A, Cetnar J, Conneran T, Desai PA, et al 2026Guideline: National Comprehensive Cancer Network 2026
Metastatic

RET fusion-positive and MET exon 14 skipping non-small cell lung cancer, FDA regulatory actions read. RET:

  • selpercatinib received accelerated approval on 8 May 2020 and pralsetinib on 4 September 2020
  • a supplement letter of 9 August 2023 converted the pralsetinib approval from accelerated to regular, and FDA's verified list shows 21 September 2022 for selpercatinib (that conversion letter was not opened). MET exon 14: capmatinib received accelerated approval on 6 May 2020 and a supplement letter of 10 August 2022 states that it fulfils the accelerated-approval commitments
  • tepotinib received accelerated approval on 3 February 2021 and a supplement letter of 15 February 2024 provides for traditional approval. Guideline documents on this topic are cited by reference only, with no recommendation summarised here
US Food and Drug Administration 2020US Food and Drug Administration 2020US Food and Drug Administration 2023US Food and Drug Administration 2020US Food and Drug Administration 2022US Food and Drug Administration 2021US Food and Drug Administration 2024FDA 2026Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Wheatley-Price P, Ismaila N, Calles Blanco A, Cetnar J, Conneran T, Desai PA, et al 2026
Metastatic

KRAS G12C, HER2 (ERBB2) and other targets, FDA actions read. KRAS G12C-mutated locally advanced or metastatic disease after at least one prior systemic therapy:

  • sotorasib (accelerated approval, 28 May 2021) and adagrasib (accelerated approval, 12 December 2022)
  • FDA's ongoing accelerated-approvals list (current as of 19 October 2026) still lists both. HER2 (ERBB2)-mutant disease: fam-trastuzumab deruxtecan after a prior systemic therapy (accelerated approval, 11 August 2022
  • still on the ongoing list)
  • zongertinib for HER2 tyrosine kinase domain-mutant non-squamous disease after prior systemic therapy (accelerated approval, 8 August 2025) and sevabertinib (accelerated approval, 19 November 2025
  • the source is a corrected letter whose effective action date remains that date). The 2026 supplement letters for zongertinib (26 February 2026) and sevabertinib (9 September 2026) describe the accelerated-approval indication without the prior-therapy phrase used in the original letters
  • what that means for the line of therapy was not checked against the labels. The ongoing list also includes telisotuzumab vedotin for high c-Met protein overexpression (14 May 2025) and zenocutuzumab for NRG1 fusions after prior systemic therapy (4 December 2024)
  • those letters were not opened. Guideline documents on this topic are cited by reference only, with no recommendation summarised here
US Food and Drug Administration 2021US Food and Drug Administration 2022US Food and Drug Administration 2022US Food and Drug Administration 2025US Food and Drug Administration 2026US Food and Drug Administration 2025US Food and Drug Administration 2026FDA 2026Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Wheatley-Price P, Ismaila N, Calles Blanco A, Cetnar J, Conneran T, Desai PA, et al 2026
Metastatic

Non-small cell lung cancer without a targetable driver, FDA regulatory actions read (the letters state first-line use for all entries except the durvalumab one; biomarker exclusions are given as each letter words them):

  • pembrolizumab as a single agent for tumors with PD-L1 TPS of 50% or more and no EGFR or ALK aberrations (24 October 2016), and with TPS of 1% or more for stage III disease not suitable for resection or definitive chemoradiation, or metastatic disease, with no EGFR or ALK aberrations (11 April 2019, per a replacement letter)
  • pembrolizumab with pemetrexed and carboplatin for non-squamous disease (accelerated approval 10 May 2017
  • the 20 August 2018 letter removes the accelerated-approval statement, adds no EGFR or ALK aberrations and states that it fulfils a postmarketing requirement) and with carboplatin and paclitaxel or nab-paclitaxel for squamous disease (30 October 2018)
  • nivolumab with ipilimumab for PD-L1 1% or more with no EGFR or ALK aberrations (15 May 2020)
  • cemiplimab as a single agent for TPS of 50% or more with no EGFR, ALK or ROS1 aberrations (22 February 2021) and with platinum-based chemotherapy for disease with no EGFR, ALK or ROS1 aberrations (8 November 2022)
  • durvalumab with tremelimumab-actl and platinum-based chemotherapy for metastatic disease with no sensitizing EGFR mutations or ALK aberrations (10 November 2022
  • this letter does not use the words "first-line"). Other first-line and later-line immunotherapy labels exist and are not itemised. Guideline documents on this topic are cited by reference only, with no recommendation summarised here. Guideline documents: ESMO non-oncogene-addicted metastatic NSCLC (Hendriks et al., Ann Oncol 2023), ASCO living guideline for stage IV disease without driver alterations (Version 2026.3.1) and NCCN NSCLC Version 9.2026
FDA 2016FDA 2019FDA 2017FDA 2018FDA 2018FDA 2020FDA 2021FDA 2022FDA 2022Guideline: Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, et al 2023Guideline: Bazhenova L, Ismaila N, Durm G, Freeman-Daily J, Horinouchi H, MacVicar GR, et al 2026Guideline: National Comprehensive Cancer Network 2026
Metastatic

Extensive-stage small cell lung cancer, first-line FDA regulatory actions read:

  • atezolizumab with carboplatin and etoposide (18 March 2019) and durvalumab with etoposide and either carboplatin or cisplatin (27 March 2020). Guideline documents: NCCN SCLC Version 1.2027 (landing-page title only), ESMO small-cell lung cancer (Dingemans et al., 2021
  • it predates the tarlatamab and lurbinectedin maintenance actions listed on this page) and the ASCO rapid recommendation update (Kalemkerian et al., 2025
  • identifier only). Guideline documents on this topic are cited by reference only, with no recommendation summarised here
FDA 2019FDA 2020Guideline: National Comprehensive Cancer Network 2026Guideline: Dingemans AC, Früh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks LE, et al 2021Guideline: Kalemkerian GP, Khurshid H, Ismaila N 2025
Maintenance
Extensive-stage small cell lung cancer after first-line induction with atezolizumab, carboplatin and etoposide: FDA approved lurbinectedin in combination with atezolizumab (or atezolizumab and hyaluronidase-tqjs) as maintenance treatment for disease that has not progressed (2 October 2025). The EMA page for Zepzelca lists the same maintenance combination with atezolizumab and a marketing authorisation issued on 29 May 2026 (opinion adopted 26 March 2026).
FDA 2025EMA 2026Guideline: National Comprehensive Cancer Network 2026
Relapsed / refractory
Extensive-stage small cell lung cancer with disease progression after platinum-based chemotherapy, regulatory actions read. Tarlatamab received accelerated approval from FDA on 16 May 2024 and a supplement letter of 19 November 2025 converted it to traditional approval; the EMA page for Imdylltra lists monotherapy for adults who require systemic therapy after progression on or after first-line platinum-based chemotherapy, with a marketing authorisation issued on 29 May 2026. Lurbinectedin received accelerated approval on 15 June 2020; FDA's withdrawn-approvals list (content current as of 5 October 2026) shows that indication withdrawn on 30 September 2026 and gives no reason. The same list shows two earlier accelerated approvals for small cell lung cancer after platinum-based chemotherapy and at least one other line, nivolumab (16 August 2018) and pembrolizumab (17 June 2019), withdrawn on 29 December 2020 and 30 March 2021. Guideline documents on this topic are cited by reference only, with no recommendation summarised here.
FDA 2024FDA 2025EMA 2026FDA 2020FDA 2026FDA 2026Guideline: National Comprehensive Cancer Network 2026Guideline: Dingemans AC, Früh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks LE, et al 2021

Trials to watch

  • IDeate-Lung02 NCT06203210

    In relapsed small cell lung cancer, does ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, differ in overall survival from treatment of physician's choice? Registry status: recruiting; randomised, open-label phase 3; no results posted on the registry record.

  • DeLLphi-306 NCT06117774

    In limited-stage small cell lung cancer that has not progressed after concurrent chemoradiotherapy, does tarlatamab improve progression-free survival or overall survival compared with placebo? Registry status: active, not recruiting; randomised, double-blind, placebo-controlled phase 3; no results posted on the registry record.

  • HARMONi-3 NCT05899608

    As first-line treatment of metastatic non-small cell lung cancer, does ivonescimab with chemotherapy differ in overall survival or progression-free survival from pembrolizumab with chemotherapy? Registry status: active, not recruiting; randomised, double-blind phase 3; no results posted on the registry record.

  • Beamion LUNG-3 NCT07195695

    After complete resection of stage II to IIIB non-small cell lung cancer with activating HER2 tyrosine kinase domain mutations, does adjuvant zongertinib improve disease-free survival compared with standard of care? Registry status: recruiting; randomised phase 3; no results posted on the registry record.

  • SUNRAY-01 NCT06119581

    In KRAS G12C-mutant, locally advanced or metastatic non-small cell lung cancer, does first-line olomorasib with pembrolizumab (PD-L1 50% or more) or with pembrolizumab, pemetrexed and platinum chemotherapy (regardless of PD-L1) improve progression-free survival compared with placebo plus the same regimen? Registry status: recruiting; randomised, double-blind phase 3 with dose-optimisation and safety lead-in parts; no results posted on the registry record.

References

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2017TreatmentTargeted

landmarkMetastatic

FLAURA: osimertinib versus gefitinib or erlotinib, first line

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

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

Since 2004, reports had linked activating EGFR mutations in lung cancer to responses to gefitinib. [1] FLAURA asked whether a newer inhibitor could do better when used first.

Osimertinib is an oral, irreversible EGFR inhibitor that acts against both the sensitising mutations and the EGFR T790M resistance mutation. [2] The FLAURA trial randomly assigned 556 people with untreated, EGFR mutation-positive advanced lung cancer to osimertinib or to a standard EGFR inhibitor, gefitinib or erlotinib, in a double-blind design. [2]

The primary result appeared online in November 2017. Median progression-free survival was 18.9 months with osimertinib and 10.2 months with the comparator inhibitors. [2] Response rates were similar (80% and 76%), and adverse events of grade 3 or higher were less frequent with osimertinib (34% versus 45%). [2]

Overall survival was immature at that point. The final analysis, published in 2019, reported median overall survival of 38.6 months with osimertinib and 31.8 months in the comparator group; the hazard ratio for death was 0.80, with a confidence interval whose upper bound reached 1.00. [3]

The US FDA approved osimertinib for first-line treatment of EGFR-mutated metastatic NSCLC in April 2018. [4]

Standard before

The trial's authors describe gefitinib and erlotinib as the standard EGFR inhibitors against which osimertinib was compared in untreated, EGFR mutation-positive disease.

What changed

The US FDA approved osimertinib on 18 April 2018 for first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.

Why it mattered

A double-blind comparison in which the third-generation inhibitor delayed progression, and in the later final analysis prolonged survival, relative to the first-generation inhibitors used as the control.

Caveats

  • The comparator arm pooled gefitinib and erlotinib; the primary endpoint was investigator-assessed PFS.
  • At the primary analysis overall survival was immature (25% maturity). The final analysis hazard ratio of 0.80 has a 95.05% confidence interval with an upper bound of 1.00 (P=0.046).
  • Only compare within the EGFR first-line lane: IPASS enrolled a clinically selected East Asian population with a chemotherapy control, and FLAURA2 and MARIPOSA use osimertinib itself as the comparator.