Trials · Topics · Thoracic Oncology
Thoracic Oncology clinical trials
157 Thoracic Oncology trials (Medical Oncology and Radiation Oncology) summarized for fellows and board review, newest first within each disease. Each summary covers design, results, toxicity and what changed in practice.
Jump to: Lung NSCLC - advanced · Lung NSCLC - EGFR · Lung NSCLC - perioperative · NSCLC · Lung NSCLC - ALK · Lung NSCLC - ROS/MET/KRAS/etc · SCLC - extensive · SCLC · Mesothelioma · Lung - Mesothelioma · Thymoma · SCLC - limited
Lung NSCLC - advanced (35)
- AdvanTIG-302 trial J Thorac Oncol 2026Ociperlimab + tislelizumab increased response rate and numerically prolonged PFS but did not improve OS over pembrolizumab (HR 0.97); the trial was stopped for...
- HARMONi-6 Lancet 2026In first-line advanced squamous NSCLC, ivonescimab plus chemotherapy significantly improved overall survival versus tislelizumab plus chemotherapy (HR 0.66) - the...
- OptiTROP-Lung05 Lancet 2026sac-TMT + pembrolizumab markedly improved PFS vs pembrolizumab alone (HR 0.35) as first-line therapy for PD-L1+ advanced NSCLC without driver alterations - the first...
- SKYSCRAPER-01 trial J Clin Oncol 2026Adding tiragolumab to atezolizumab did not produce a statistically significant improvement in either co-primary endpoint in previously untreated PD-L1-high advanced...
- SKYSCRAPER-06 trial JAMA Oncol 2026Tiragolumab + atezolizumab + chemotherapy was not superior - and trended inferior on both PFS and OS - to pembrolizumab + chemotherapy in first-line nonsquamous...
- TROP2-Targeted ADCs in NSCLC: Expert Consensus (2026 Edition) 2026TROP2 ADCs show substantial antitumor activity and survival benefit; standardized clinical use and safety management protocols are essential for optimal outcomes....
- ZEAL-1L trial J Thorac Oncol 2026Adding niraparib to pembrolizumab maintenance did not improve efficacy in biomarker-unselected advanced NSCLC (PFS HR 1.00). Definitively negative phase 3 that...
- PEARL trial JTO 2025Durvalumab monotherapy did not improve survival over chemotherapy in PD-L1 ≥25% NSCLC, failing to replicate pembrolizumab monotherapy benefit in comparable populations.
- POSEIDON trial JTO 2025Adding limited-course tremelimumab to durvalumab + chemo produced durable long-term survival benefit, roughly doubling 5-year OS versus chemo, with manageable added...
- Schram AM et al, NEJM, 2025, eNRGy trial 2025Zenocutuzumab produced durable responses in NRG1 fusion-positive NSCLC and pancreatic cancer with a manageable toxicity profile.
- TROP2 ADCs in NSCLC: Clinical Overview Cancer Treat Rev 2025TROP2 ADCs offer multiple mechanisms and efficacy profiles; unique linker/payload characteristics inform mechanism of action, dosing, and management. Sequential use...
- TROPION-Lung05 JCO 2025Dato-DXd showed encouraging, durable activity in heavily pretreated NSCLC with actionable alterations, greatest in the EGFR-mutant subgroup; safety consistent with...
- DESTINY-PanTumor02 JCO 2024T-DXd showed meaningful activity across HER2-expressing tumors including NSCLC, with response enriched in IHC 3+ disease, supporting HER2 expression as a...
- EVOKE-01 Trial JCO 2024Sacituzumab govitecan showed a numerical OS trend over docetaxel in pretreated NSCLC with a more favorable safety profile, but narrowly missed the OS endpoint.
- TROPION LUNG 01 Dato-DXd in 2L NSCLC JCO 2025Dato-DXd modestly improved PFS over docetaxel (driven by non-squamous histology) without an OS benefit; squamous patients did worse. A TROP2 QCS-NMR biomarker...
- PAPILLON trial N Engl J Med 2023First-line amivantamab plus chemotherapy markedly prolonged PFS versus chemotherapy alone in EGFR exon 20 insertion NSCLC, establishing a new standard of care.
- 2L Lung-MAP trial, rami+pembro JCO 2022Ramucirumab plus pembrolizumab significantly improved OS versus SOC in NSCLC progressing ≥3 months after prior immunotherapy, without a PFS or ORR advantage.
- EMPOWER-Lung 3 Nat Med 2022Cemiplimab + chemotherapy improved OS vs chemotherapy alone in 1L NSCLC regardless of PD-L1 level (HR 0.71), establishing an all-comer first-line option. Benefit was...
- CheckMate 9LA trial Lancet Onc 2021Nivolumab + ipilimumab + 2 cycles of chemotherapy significantly improved OS vs chemotherapy alone in first-line advanced NSCLC, regardless of PD-L1 or histology....
- EMPOWER-Lung 1 Lancet 2021Cemiplimab significantly improved OS vs chemotherapy in PD-L1 ≥50% 1L NSCLC (HR 0.68), establishing it as an alternative to pembrolizumab monotherapy in this...
- Impower110 trial NEJM 2020First-line atezolizumab monotherapy significantly improved OS in NSCLC with high PD-L1 expression, with less toxicity than chemotherapy.
- MYSTIC trial, durva+tremelimumab JAMA Onc 2020MYSTIC did not meet its primary OS or PFS endpoints in PD-L1 TC ≥25%. Exploratory analyses suggested OS benefit with durvalumab + tremelimumab in patients with TMB...
- KEYNOTE-042 Lancet 2019First-line pembrolizumab monotherapy improved OS across PD-L1 TPS ≥1%, ≥20%, and ≥50%, but benefit was driven by high expressers; the 1-49% subgroup derived no clear...
- IMpower150 NEJM 2018Atezolizumab + bevacizumab + carboplatin + paclitaxel (ABCP) significantly improved PFS and OS versus BCP in 1L metastatic non-squamous NSCLC, with benefit regardless...
- KEYNOTE-189 NEJM 2018Pembrolizumab + platinum/pemetrexed in metastatic nonsquamous NSCLC significantly prolonged OS and PFS across all PD-L1 strata, including PD-L1 <1%.
- KEYNOTE-407 NEJM 2018Adding pembrolizumab to carboplatin-taxane significantly improved OS and PFS in metastatic squamous NSCLC across all PD-L1 strata.
- OAK Lancet 2017Atezolizumab significantly improved OS vs docetaxel in 2L+ NSCLC (HR 0.73), with benefit observed regardless of PD-L1 expression or histology. OS improvement without...
- KEYNOTE-024 NEJM 2016First trial to show OS benefit with first-line anti-PD-1 monotherapy in NSCLC (TPS ≥50%), with a favorable AE profile vs chemotherapy.
- CheckMate 017 NEJM 2015Nivolumab significantly improved OS vs docetaxel in previously treated squamous NSCLC (HR 0.59), with markedly lower toxicity. PD-L1 expression did not predict...
- CheckMate 057 NEJM 2015Nivolumab significantly improved OS vs docetaxel in previously treated non-squamous NSCLC (HR 0.73). Unlike CheckMate 017, PD-L1 predicted benefit - PD-L1 ≥10% OS HR...
- SQUIRE Trial gem/cis+necitumumab in SQ-NSCLC Lancet Oncol 2015Adding necitumumab to cisplatin/gemcitabine modestly improved OS in advanced squamous NSCLC but at the cost of meaningful toxicity.
- 2L Doce +/- rami after POD on chemo, REVEL trial Lancet 2014Adding ramucirumab to docetaxel modestly improved OS and PFS as second-line therapy in advanced NSCLC; reasonable for patients with robust performance status.
- Scagliotti trial JCO 2008Cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine overall with less toxicity, but the histology interaction (worse OS in squamous, better in nonsquamous)...
- 2L Pemetrexed after POD on chemo JCO 2004Pemetrexed is non-inferior to docetaxel in 2L advanced NSCLC with a markedly better hematologic toxicity profile; benefit is confined to non-squamous histology.
- 2L Docetaxel after POD on chemo JCO 2000Docetaxel 75 mg/m2 (but not 100 mg/m2) improved survival and quality of life vs best supportive care, establishing it as the standard second-line agent for NSCLC.
Lung NSCLC - EGFR (35)
- AENEAS2 trial Lancet Oncol 2026Adding platinum-pemetrexed to first-line aumolertinib extended median PFS by ~10 months (28.9 vs 18.9mo; HR 0.47) in EGFR-mutant advanced NSCLC, at the cost of...
- CHRYSALIS-2: Amivantamab in EGFR Exon 20 Insertion NSCLC J Formos Med Assoc 2026Amivantamab demonstrates substantial benefit over real-world second-line therapies in EGFR exon 20-mutated NSCLC; addresses significant unmet need in this population...
- HARMONi trial Lancet Oncol 2026Adding ivonescimab to platinum-pemetrexed after 3rd-generation EGFR-TKI failure roughly halved the risk of progression (HR 0.52), with a 2.8-month OS gain that did...
- HARMONi-A trial JAMA 2026With mature follow-up, adding the PD-1/VEGF bispecific ivonescimab to platinum-pemetrexed significantly improved OS (16.8 vs 14.1 mo; HR 0.74) after EGFR-TKI failure...
- TOP trial JAMA 2026In EGFR-mutated advanced NSCLC with concurrent TP53 mutations, first-line osimertinib plus chemotherapy more than doubled median PFS vs osimertinib alone (34.0 vs...
- WU-KONG28 trial NEJM 2026First-line sunvozertinib, an oral EGFR exon20ins-active TKI, significantly improved PFS, ORR and DoR vs platinum-doublet chemotherapy in advanced EGFR exon20ins...
- Amivantamab in EGFR Exon 20-Mutated NSCLC: Brazil Health System Analysis JCO Glob Oncol 2025Delayed SUS incorporation of amivantamab may result in over 1,000 preventable deaths among EGFR exon 20-mutated NSCLC patients in Brazil; urgent real-world evidence...
- EGFR-Mutated NSCLC Post-TKI: Network Meta-Analysis of Regimens Ther Adv Med Oncol 2025CT+ivonescimab is optimal for PFS with acceptable safety; CT+amivantamab+lazertinib has the highest ORR/DCR but elevated grade ≥3 AEs; CT+amivantamab and...
- FLAURA2 NEJM 2025Osimertinib + platinum-pemetrexed improved both PFS (HR 0.62) and OS (HR 0.77, P=.02) vs osimertinib monotherapy in 1L EGFR+ mNSCLC. The OS benefit of 9.9 months...
- TOP trial, Osi + Chemo vs Osi (EGFR/TP53 co-mutated NSCLC) Sci Rep 2025Adding platinum-pemetrexed chemotherapy to first-line osimertinib in EGFR/TP53 co-mutated advanced NSCLC produced a numerical PFS and response-rate advantage that did...
- ATTLAS trial JCO 2024In EGFR/ALK+ NSCLC post-TKI, adding atezolizumab + bevacizumab to chemo significantly improved PFS and response, especially at higher PD-L1. OS was similar...
- EGFR-Mutated NSCLC Treatment Sequencing Review Med (NY) 2024Ivonescimab represents a novel second-line option addressing the limitations of single-agent checkpoint inhibitors in EGFR-mutated disease. Bispecific targeting of...
- HARMONI-A - ivonescimab JAMA 2024Ivonescimab plus chemotherapy significantly improved PFS over chemotherapy alone in EGFR-TKI-treated advanced NSCLC, with a tolerable safety profile.
- KEYNOTE-789 trial JCO 2024Adding pembrolizumab to chemotherapy did not significantly improve PFS or OS in EGFR-TKI-resistant NSCLC. Chemo-immunotherapy offers no clear benefit here...
- MARIPOSA trial Ann Oncol 2024Amivantamab-lazertinib is the first chemotherapy-free regimen to improve OS over osimertinib in first-line EGFR-mutant advanced NSCLC, supporting its role as a new...
- MARIPOSA-2 Trial Ann Oncol 2024Adding amivantamab to chemotherapy after osimertinib progression significantly prolonged PFS and nearly doubled response rates, establishing a new second-line...
- PALOMA-3 trial JCO 2024SC amivantamab + lazertinib was noninferior to IV in efficacy, markedly reduced infusion reactions and administration time, and improved convenience - supporting SC...
- WU-KONG6 (sunvozertinib, DZD9008) Lancet Respir Med 2023Oral sunvozertinib produced clinically meaningful confirmed responses (ORR 61%) with manageable toxicity in platinum-pretreated EGFR exon 20 insertion NSCLC...
- EGFR ex20, POSITION20 trial, high-dose osi Lung Cancer 2022High-dose osimertinib (160 mg) demonstrated modest activity in EGFR exon20 insertion+ NSCLC.
- Progression after 1L Osimertinib, phase 1/2 trials 2022Multiple novel agents (HER3-DXd, amivantamab + lazertinib, teliso-V + osimertinib) show activity after osimertinib failure, with responses partly tracking resistance...
- EGFR ex20, 2L Mobocertinib JAMA Onc 2021Mobocertinib produced confirmed ORR 28% with mDOR 17.5mo and mOS 24.0mo in platinum-pretreated EGFR exon20 insertion NSCLC, an active oral option in this...
- EGFR ex20, CHRYSALIS trail, 2L Amivantamab JCO 2021Amivantamab provided durable responses as a second-line option for EGFR exon20 insertion+ NSCLC.
- Erlotinib +/- Bevacizumab trials 2021Adding bevacizumab to erlotinib improved PFS but not OS in first-line EGFR-mutant NSCLC; consistent with the class pattern that EGFR+VEGF combinations improve PFS...
- EVAN JAMA Oncol 2021Adjuvant erlotinib demonstrated markedly improved 2-year EFS (HR 0.27) and exploratory OS benefit vs platinum-doublet chemotherapy in resected stage IIIA EGFR-mutated...
- ADAURA trial, adjuvant Osimertinib NEJM 2020Adjuvant osimertinib for resected stage IB-IIIA EGFR-mutated NSCLC significantly improved DFS and, at the 5-yr update, OS.
- NEJ009 trial, gefitinib +/- chemo JCP 2020Adding carboplatin/pemetrexed to gefitinib significantly improved PFS and OS in EGFR-mutated advanced NSCLC. A treatment option balanced against increased toxicity.
- WJOG9717L7 trial, Osi +/- ramucirumab JTO 2021Adding ramucirumab to osimertinib did not significantly improve PFS first-line in EGFR-mutant NSCLC; the primary endpoint was not met and toxicity was increased.
- RELAY trial, Erlotinib +/- Ramucirumab Lancet Oncol 2019Adding ramucirumab to erlotinib improved PFS but not (mature) OS in first-line EGFR-mutant NSCLC; consistent with EGFR+VEGF combinations improving PFS only.
- ADJUVANT/CTONG1104 Lancet Oncol 2018Gefitinib significantly improved DFS vs platinum-doublet chemotherapy in EGFR-mutated stage II-IIIA NSCLC (HR 0.60), with markedly better tolerability. No OS benefit...
- FLAURA trial NEJM 2018First-line osimertinib was superior to first-generation TKIs (erlotinib/gefitinib) in PFS and OS for advanced EGFR-mutated NSCLC, establishing it as a preferred...
- ARCHER 1050 trial, dacomitinib vs gefitinib Lancet Onc 2017Dacomitinib improved PFS and OS vs gefitinib first-line in EGFR ex19del/L858R advanced NSCLC, but use is limited by high toxicity and frequent dose reductions.
- LUX-Lung 1, afatinib after progression on TKI Lancet Onc 2012Afatinib improved PFS and ORR but not OS in patients progressing after chemotherapy and a first-generation EGFR TKI; the primary OS endpoint was not met.
- Erlotinib vs chemotherapy in 1st line 2011Erlotinib improved PFS but not OS (likely from crossover) vs chemotherapy in first-line EGFR-mutated advanced NSCLC; historical evidence establishing TKI over...
- Afatinib vs chemotherapy in 1st line 2010Afatinib significantly improved PFS over chemotherapy in EGFR-mutated advanced NSCLC, with OS benefit in the ex19del subgroup; historical first-line evidence.
- Gefitinib vs chemotherapy in 1st line 2010Gefitinib improved PFS over chemotherapy in EGFR-mutated advanced NSCLC (and was harmful in EGFR-wild-type); historical evidence establishing biomarker-selected TKI...
Lung NSCLC - perioperative (18)
- ANVIL trial JAMA 2026Adjuvant nivolumab after upfront surgery and planned adjuvant chemotherapy/RT did not improve DFS overall or in PD-L1 ≥50% resected NSCLC. A definitive negative...
- KEYNOTE-671 trial (5-year update) Ann Oncol 2026At 5 years, perioperative pembrolizumab nearly doubled EFS and continued to improve OS versus neoadjuvant chemotherapy and surgery alone. The durable, clinically...
- Nivolumab + CCRT ± Ipilimumab vs Durvalumab in Stage III NSCLC Nat Cancer 2026Substituting nivolumab + CCRT followed by nivolumab ± ipilimumab consolidation for the PACIFIC regimen did not improve PFS or OS in unresectable stage III NSCLC and...
- 77T trial N Engl J Med 2024Perioperative nivolumab significantly improved EFS and pathological response vs chemotherapy alone in resectable NSCLC, without new safety concerns. Benefit was most...
- Adjuvant durvalumab - LBA48 CCTG BR.31 trial Ann Oncol 2024Adjuvant durvalumab did not significantly prolong DFS or OS in resected NSCLC. BR.31 is a negative trial, indicating adjuvant PD-L1 inhibition after chemotherapy...
- AEGEAN trial N Engl J Med 2023Perioperative durvalumab with neoadjuvant chemotherapy significantly improved EFS and pCR in resectable NSCLC, with a safety profile consistent with the known effects...
- Checkmate 816 trial JCO 2025Neoadjuvant nivolumab + ipilimumab showed potential long-term benefit and higher pCR vs chemotherapy with fewer high-grade toxicities, though early progression and...
- KEYNOTE-671 trial Lancet 2024Perioperative pembrolizumab significantly improved both EFS and OS vs chemotherapy alone in early-stage resectable NSCLC, with a manageable safety profile.
- LAURA trial NEJM 2024Osimertinib consolidation after definitive chemoradiotherapy dramatically improved PFS (39.1 vs 5.6mo) in unresectable stage III EGFR-mutated NSCLC. OS data remain...
- LUSTRE trial JAMA Oncol 2024SBRT did not significantly improve local control or survival over hypofractionated RT for medically inoperable stage I NSCLC; both achieved ~90+% 3-yr local control....
- NADIM trial Lancet Oncol 2024Neoadjuvant chemotherapy plus nivolumab followed by adjuvant nivolumab produced durable 5-yr PFS (65%) and OS (69%) in resectable stage IIIA NSCLC. pCR was strongly...
- NAOS trial JCO 2024Neoadjuvant osimertinib monotherapy produced low pathological response (MPR ~15%). Although safe and not compromising resection, the modest tumor kill indicates...
- NADIM II NEJM 2023Perioperative nivolumab + chemotherapy resulted in significantly higher pCR (37% vs 7%) and improved PFS vs chemotherapy alone in resectable stage III NSCLC. The OS...
- KEYNOTE-091/PEARLS Lancet Oncol 2022Adjuvant pembrolizumab improved DFS in the all-comers resected NSCLC population (HR 0.76, P=.0014), but the hierarchical primary analysis technically failed because...
- Stage III NSCLC Immunotherapy Review (Durvalumab et al) Ann Oncol 2022Adjuvant durvalumab is standard, but modest (~33%) long-term DFS indicates need for novel strategies: induction immunotherapy, combination agents, biomarker-driven...
- IMPOWER 010 trial, adj atezo Lancet 2021Adjuvant atezolizumab after chemotherapy improved DFS in resected stage II-IIIA NSCLC, with greatest benefit in PD-L1≥1% tumors, establishing a role for adjuvant...
- NEOSTAR Trial 2021Neoadjuvant nivolumab + ipilimumab enhanced pathologic responses, tumor immune infiltrates, and immunologic memory vs nivolumab alone in operable NSCLC.
- ANITA Lancet Oncol 2006Adjuvant vinorelbine + cisplatin significantly improved OS in resected NSCLC (HR 0.80), establishing platinum-based doublet chemotherapy as standard adjuvant...
NSCLC (16)
- SKYSCRAPER-03 trial Ann Oncol 2026Tiragolumab + atezolizumab consolidation was not superior to durvalumab after chemoradiation for unresectable stage III NSCLC - PFS and OS were essentially identical....
- SWOG/NRG S1914 trial Lancet 2026Adding atezolizumab to SBRT did not improve overall survival or PFS in high-risk, early-stage inoperable NSCLC and increased toxicity. This is the first fully...
- CheckMate 227 NEJM 2019Nivolumab + ipilimumab significantly improved OS vs chemotherapy in PD-L1 ≥1% advanced NSCLC (HR 0.79, p=0.007) with markedly longer response durability. Activity was...
- CHISEL Lancet Oncol 2019SABR significantly reduced local failure risk by approximately 75% (HR 0.25) compared to conventional fractionated RT in inoperable stage I NSCLC, with comparable...
- Oligometastatic NSCLC Trial J Clin Oncol 2019Local consolidative therapy to all sites of oligometastatic NSCLC after first-line systemic therapy significantly improved both PFS (HR 0.35) and OS (HR 0.37)...
- RTOG 0813 J Clin Oncol 201960 Gy in 5 fractions (12 Gy/fraction) was established as the recommended SBRT dose for centrally located NSCLC, with acceptable toxicity and high local control (88.8%...
- PACIFIC N Engl J Med 2018Durvalumab consolidation after concurrent CRT significantly improved both PFS (HR 0.51) and OS (HR 0.68) in unresectable stage III NSCLC - the first regimen to show...
- NCDB PORT Analysis J Clin Oncol 2015PORT was associated with a significant survival benefit (HR 0.77) for pN2 NSCLC after resection in this large registry analysis, providing renewed support for PORT...
- RTOG 0617 Lancet Oncol 2015Dose escalation to 74 Gy paradoxically worsened OS compared to standard 60 Gy in stage III NSCLC treated with concurrent chemoRT (HR 1.38, p=0.004). Cetuximab added...
- STARS-ROSEL Lancet Oncol 2015In this pooled analysis, SABR was associated with superior 3-year OS (95% vs 79%, HR 0.14) and dramatically lower grade ≥3 toxicity compared to lobectomy in operable...
- RTOG 0236 JAMA 2010SBRT 18 Gy × 3 fractions achieved 97.6% local tumor control at 3 years for medically inoperable peripheral stage I NSCLC - vastly superior to historical conventional...
- IMPT vs IMRT NSCLC Dosimetry IJROBP 2010IMPT achieves significantly lower dose to lungs, heart, and esophagus compared to photon IMRT for locally advanced NSCLC at equivalent tumor coverage. The dosimetric...
- Intergroup 0139 Lancet 2009Adding surgery to concurrent chemoRT did not improve OS vs definitive CRT alone in stage IIIA(N2) NSCLC (HR 0.87, p=0.24). Modest PFS improvement was offset by high...
- HOG LUN 01-24 J Clin Oncol 2008Pemetrexed consolidation after concurrent CRT provided no OS or PFS benefit over observation in stage III NSCLC, and caused significant excess toxicity. Consolidation...
- Intergroup 0160 J Clin Oncol 2007Trimodality therapy (cisplatin/etoposide + 45 Gy → surgery) achieves high complete resection rates (76%) and 5-year OS of 44% for superior sulcus NSCLC - markedly...
- Fried RT Timing Systematic Review J Clin Oncol 2004Early thoracic RT significantly improved 2-yr OS vs late RT in limited SCLC (RR 1.17), with greatest benefit in trials using hyperfractionated RT and platinum-based...
Lung NSCLC - ALK (11)
- ECOG-ACRIN E4512 trial Lancet Respir Med 2026Adjuvant crizotinib did not improve DFS versus observation in resected early-stage ALK-positive NSCLC. The trial was underpowered because accrual stopped early after...
- ELEVATE N Engl J Med 2026Adjuvant ensartinib for 24 months reduced the risk of recurrence or death by 80% versus placebo (HR 0.20) after resection and chemotherapy in ALK-positive NSCLC....
- ALINA NEJM 2024Adjuvant alectinib produced a dramatic DFS improvement vs platinum chemotherapy in resected ALK-positive NSCLC (HR 0.24; 2-yr DFS 93.8% vs 63.0%), the largest...
- CROWN trial JCO 2024At 5 years, lorlatinib delivered unprecedented PFS (60% event-free) and intracranial control vs crizotinib in advanced ALK-positive NSCLC, setting a new 1L benchmark...
- eXalt3 JAMA Oncol 2021Ensartinib delivered superior PFS (HR 0.51) and markedly better intracranial activity (ORR 64% vs 21%) vs crizotinib in 1L ALK-positive NSCLC, supporting it as an...
- 2L Lorlatinib, phase II trials Lancet Oncol 2018Lorlatinib showed significant activity in ALK-positive NSCLC progressing on crizotinib or a 2nd-generation TKI, including durable CNS responses, supporting its role...
- ALTA-1L , briga vs crizo NEJM 2018Brigatinib significantly improved PFS, ORR, and intracranial response over crizotinib in treatment-na ve ALK-positive NSCLC, supporting brigatinib as a first-line option.
- Alex trial, alect vs crizo NEJM 2017Alectinib had superior efficacy and lower toxicity vs crizotinib in untreated advanced ALK-positive NSCLC, establishing it as a first-line standard.
- ASCEND-4 trial, cerit vs chemo Lancet 2017Ceritinib significantly improved PFS and ORR vs chemotherapy in treatment-na ve ALK-positive NSCLC, validating first-line ALK TKI therapy.
- J-ALEX Lancet 2017Alectinib demonstrated superior PFS (HR 0.34) and substantially better tolerability vs crizotinib in Japanese ALK-positive NSCLC, establishing it as the preferred ALK...
- PROFILE 1014 trial, crizot vs chemo NEJM 2014Crizotinib significantly improved PFS and response rate vs chemotherapy in treatment-na ve ALK-positive NSCLC; the related second-line trial (PROFILE 1007, Shaw AT et...
Lung NSCLC - ROS/MET/KRAS/etc (11)
- LIBRETTO-432 N Engl J Med 2026Adjuvant selpercatinib produced a large, clinically meaningful improvement in event-free survival (HR 0.17) versus placebo in early-stage RET fusion-positive NSCLC...
- KRYSTAL-12 Lancet 2025Adagrasib significantly improved PFS vs docetaxel in previously treated KRAS G12C+ NSCLC (HR 0.58), the first phase III trial demonstrating PFS benefit for adagrasib...
- TRIDENT-1 NEJM 2024Repotrectinib produced high, durable systemic and intracranial responses in ROS1+ NSCLC regardless of prior TKI, with activity against G2032R; toxicity mainly...
- CODEBREAK 200 Lancet 2023In previously treated KRAS-G12C-mutated advanced NSCLC, sotorasib significantly prolonged PFS vs docetaxel with a more favorable safety profile, supporting it as a...
- DESTINY-Lung02 JCO 2023T-DXd produced durable responses in previously treated HER2-mutant NSCLC at both doses; 5.4 mg/kg offered the more favorable benefit-risk balance (particularly for...
- LIBRETTO-431 NEJM 2023Selpercatinib significantly prolonged PFS and improved ORR vs platinum chemotherapy ± pembrolizumab in first-line RET fusion-positive NSCLC, confirming it as...
- Entrectinib in ROS1+ NSCLC 2020Entrectinib produced durable systemic and intracranial responses in ROS1 fusion-positive advanced NSCLC, supporting its use particularly in patients with CNS metastases.
- GEOMETRY mono-1 NEJM 2020Capmatinib showed substantial activity in MET exon 14-skipping NSCLC, greatest in treatment-naive patients; MET-amplified activity tracked with gene copy number....
- LIBRETTO-001 NEJM 2020Selpercatinib demonstrated highly durable responses in RET fusion-positive NSCLC across all prior treatment settings, including robust CNS activity, establishing it...
- 2L Lorlatinib in ROS1+ NSCLC LAncet Onc 2019Lorlatinib showed meaningful systemic and intracranial activity in ROS1-positive NSCLC, including in patients who progressed on prior crizotinib, supporting its use...
- Profile 1001 trial, crizotinib in ROS1+ NEJM 2014Crizotinib produced durable responses and prolonged survival in ROS1-rearranged advanced NSCLC, establishing it as an effective targeted therapy for this molecular...
SCLC - extensive (9)
- TAISHAN-302 (tambotatug pelitecan vs topotecan, 2L SCLC) NEJM 2026In relapsed SCLC after platinum, the B7-H3 ADC tambotatug pelitecan improved OS by ~4 mo (HR 0.46), PFS (HR 0.29) and ORR (59% vs 10%) over topotecan, with fewer...
- DeLLphi-304 NEJM 2025Tarlatamab significantly improved OS vs standard chemotherapy as second-line treatment for ES-SCLC, establishing a new standard of care in DLL3-expressing SCLC after...
- IMforte Lancet 2025Lurbinectedin + atezolizumab maintenance significantly prolonged both PFS and OS vs atezolizumab alone in ES-SCLC responders, at the cost of more, mostly hematologic...
- EXTENTORCH trial JAMA Oncol 2024Adding toripalimab to first-line etoposide-platinum significantly improved both PFS and OS in ES-SCLC, consistent with other PD-(L)1 inhibitors, supporting...
- DeLLphi-301 NEJM 2023Tarlatamab produced durable responses in heavily pretreated R/R SCLC with DLL3 expression, the first bispecific T-cell engager approval in SCLC and a novel mechanism...
- CASPIAN Lancet Oncol 2021First-line durvalumab + platinum-etoposide improved OS vs chemotherapy in extensive-stage SCLC; adding tremelimumab did not significantly improve outcomes and...
- KEYNOTE-604 JCO 2020Pembrolizumab + chemotherapy significantly improved PFS in ES-SCLC but failed to meet the prespecified OS significance boundary, a statistically negative trial for...
- Lurbinectedin monotherapy (PM1183) Lancet Oncol 2020Lurbinectedin monotherapy was active in second-line SCLC (ORR 35%) with a manageable, mainly haematologic safety profile, offering an option for a population with few...
- Impower 133 NEJM 2018Adding atezolizumab to carboplatin/etoposide significantly improved OS and PFS in first-line extensive-stage SCLC, establishing chemoimmunotherapy as a new standard...
SCLC (7)
- CONVERT Lancet Oncol 2017Twice-daily RT (45 Gy/30 fx BID) was not inferior to once-daily RT (66 Gy/33 fx QD) for limited SCLC - since the trial was designed to show superiority of QD and...
- Takahashi PCI vs Observation Lancet Oncol 2017PCI did not improve and may have worsened OS compared to MRI surveillance in extensive SCLC patients with confirmed MRI-negative brains (HR 1.27, p=0.094). This trial...
- Slotman Thoracic RT ES-SCLC Lancet 2015Thoracic RT did not significantly improve the primary endpoint of 1-year OS in extensive SCLC after chemoresponse (HR 0.84, p=0.066), but significantly improved...
- EORTC 08993 N Engl J Med 2007PCI significantly reduced symptomatic brain metastases (HR 0.27) and improved both OS and disease-free survival in extensive SCLC responders. This was the first phase...
- CALGB 39808 Int J Radiat Oncol Biol Phys 2004Accelerated hyperfractionated RT delivering 70 Gy over 7 weeks was feasible in limited SCLC with 2-year OS of 48%, comparable to or slightly better than INT-0096...
- INT-0096 N Engl J Med 1999Twice-daily accelerated (hyperfractionated) RT (45 Gy/30 fx BID) significantly improved median OS (23 vs 19 months) and 5-year OS (26% vs 16%) compared to once-daily...
- PCI Meta-Analysis N Engl J Med 1999PCI in SCLC patients achieving complete remission reduces brain metastasis risk by 54% and improves 3-yr OS by 5.4 percentage points. PCI is established as standard...
Mesothelioma (6)
- IMPRINT J Clin Oncol 2016Hemithoracic IMRT after P/D (IMPRINT) is safe with only 7.4% grade ≥3 RP, avoiding the fatal contralateral lung toxicity seen with EPP + IMRT. Median OS 23.7 months...
- EORTC 08031 Eur Respir J 2010Trimodality therapy for MPM was feasible but completed within strict protocol timelines in only 42%. Median OS 18.4 months is consistent with other selected...
- MDACC IMRT MPM Toxicity Int J Radiat Oncol Biol Phys 2007Fatal pulmonary toxicity occurred in 9.5% within 6 months of IMRT after EPP, with contralateral lung V20 the sole independent predictor of pulmonary- and...
- MSKCC 3D-CRT Mesothelioma Technique Int J Radiat Oncol Biol Phys 2003Hemithoracic 3D-CRT delivering 54 Gy after EPP is technically feasible with acceptable toxicity. The combined photon/electron technique with customized blocking...
- MSKCC Phase II Mesothelioma J Thorac Cardiovasc Surg 2001High-dose hemithoracic RT (54 Gy) after complete resection reduced local recurrence in MPM while being well tolerated. Median OS 33.8 months for stage I-II exceeded...
- Harvard Mesothelioma Trimodality J Thorac Cardiovasc Surg 1999Trimodality therapy for MPM was feasible with 3.8% perioperative mortality and 5-yr OS 15% overall. Patients with all 3 favorable factors had 46% 5-yr OS...
Lung - Mesothelioma (4)
- BEAT-meso, ETOP 13-18 Ann Oncol 2025Adding atezolizumab improved PFS but did NOT significantly improve OS in the overall population. A significant OS and PFS benefit was seen in non-epithelioid...
- CHECKMATE 743 trial, ipi/nivo for mesothelioma Lancet 2021First-line nivolumab + ipilimumab significantly improved OS vs platinum-pemetrexed in unresectable malignant pleural mesothelioma, with the largest benefit in...
- Confirm Trial Lancet Onc 2021Nivolumab improved PFS and OS vs placebo in relapsed malignant mesothelioma after ≥2 prior lines of chemotherapy, supporting single-agent immunotherapy in the...
- MAPS Lancet 2016Adding bevacizumab to pemetrexed-cisplatin significantly improved OS (18.8 vs 16.1mo, HR 0.77) and PFS in unresectable MPM, the first phase 3 trial to improve upon...
Thymoma (4)
- Jackson PORT Thymoma NCDB J Thorac Oncol 2017PORT was associated with superior OS in thymoma (HR 0.72) on multivariable and propensity score analyses, with greatest benefit for stage IIB, stage III, and positive...
- Ahmad Thymic Carcinoma International Analysis J Thorac Cardiovasc Surg 2015R0 resection and adjuvant RT were independently associated with improved OS and RFS in thymic carcinoma on multivariable analysis. Median OS of 6.6 years in this...
- Forquer SEER Thymoma Int J Radiat Oncol Biol Phys 2010PORT appears to have no benefit and may be harmful for localized (stage I) thymoma/TC, while possibly improving OS for regional disease (stage II-III). However, PORT...
- Kundel Adjuvant RT Thymoma Am J Clin Oncol 2007Adjuvant RT after surgery for invasive thymoma is associated with long-term DFS and OS. Doses >45 Gy were associated with significantly better OS and DFS vs ≤45 Gy...
SCLC - limited (1)
- ADRIATIC trial NJEM 2024Consolidation durvalumab after cCRT significantly improved OS and PFS vs placebo in limited-stage SCLC with acceptable tolerability, establishing a new standard of...