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Introduction: The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR and ALK wild-type metastatic NSCLC (mNSCLC). D+CT had a trend for OS improvement versus CT that did not reach statistical significance. This article reports prespecified OS analyses after long-term follow-up (median >5 y)., Methods: A total of 1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell programmed cell death ligand-1 (PD-L1) expression (≥50% versus <50%), disease stage (IVA versus IVB), and tumor histologic type (squamous versus nonsquamous). Serious adverse events were collected during follow-up., Results: After a median follow-up of 63.4 months across all arms, T+D+CT had sustained OS benefit versus CT (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.89; 5-y OS: 15.7% versus 6.8%). OS improvement with D+CT versus CT (HR = 0.84, 95% CI: 0.72-1.00; 5-y OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR = 0.69, 95% CI: 0.56-0.85) versus squamous (HR = 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 tumor cell less than 1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified., Conclusions: After a median follow-up of more than 5 years, T+D+CT had durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease., Competing Interests: Disclosure Peters has received grants (paid to institution) from Amgen, Arcus, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche/Genentech, GlaxoSmithKline, iTeos, Merck Sharp & Dohme, Merck Serono, Mirati, PharmaMar, Promontory Therapeutics, and Seattle Genetics; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events (paid to institution) from AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Foundation Medicine, GlaxoSmithKline, Illumina, Imedex, Ipsen, Medscape, Merck Sharp & Dohme, Mirati, MJH Life Sciences, Novartis, Peerview, Pfizer, RTP, and Takeda; and has participation on a data safety monitoring board or advisory board (payment to institution) for AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Fishawack, Foundation Medicine, F-Star, Genzyme, Gilead, GlaxoSmithKline, Hutchmed, Illumina, Imedex, Incyte, Ipsen, IQVIA, iTeos, Janssen, Medscape, Medtoday, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati, MJH Life Sciences, Novartis, Novocure, Nykode Therapeutics, OncologyEducation, Peerview, Pharma Mar, Pfizer, Promontory Therapeutics, Regeneron, RMEI, RTP, Sanofi, Seattle Genetics, and Takeda. Cho reports receiving research funding from MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp., GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center, and Vertical Bio AG; receiving royalties from Champions Oncology, Crown Bioscience, Imagen, and PearlRiver Bio GmbH; receiving consulting fees from Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi; receiving payment or honoraria for presentations from ASCO, AstraZeneca, Guardant, Roche, ESMO, International Association for the Study of Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, Merck Sharp & Dohme, The Chinese Thoracic Oncology Society, and Pfizer; having scientific advisory board participation for Kanaph Therapeutics Inc., Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc., J INTS Bio, Therapex Co., Ltd., Gilead, and Amgen; having membership of the board of directors for J INTS BIO; having stock ownership in TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp., and J INTS BIO; having employment with Yonsei University Health System; and being a founder of DAAN Biotherapeutics. Alatorre-Alexander has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, and Roche; received support for attending meetings and/or travel from AstraZeneca, Merck Sharp & Dohme, and Roche; and participated on a data safety monitoring board or advisory board for Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, and Roche. Geater has received research funding (paid to institution) from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, and Roche; received honoraria from AstraZeneca and Boehringer Ingelheim; and performed an advisory role for Merck Sharp & Dohme and Pfizer. Laktionov has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AstraZeneca, Biocad, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche AG, and has participated on a data safety monitoring board or advisory board for AstraZeneca, Biocad, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and Roche AG. Kim has received grants (paid to institution) from Yuhan and support for attending an investigator meeting from AstraZeneca. Hussein has received consulting fees from IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, Bristol-Myers Squibb, AstraZeneca, Mirati Therapeutics, Exelixis, Biopharma, Oncocyte, Aptitude Health, IntrinsiQ, GIntrinsiQ, National Community Oncology Dispensing Association, Integra PrescisionQ, AbbVie, and CTI BioPharma Corp. Araujo has received grants from Lilly, Boehringer, Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Pfizer, AstraZeneca, Novartis, and Merck; consulting fees from Merck Sharp & Dohme, Roche, AstraZeneca, Bristol-Myers Squibb, Lilly, Illumina, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Boehringer, Merck, Roche, Pfizer, and Lilly; and support for attending meetings and/or travel from Daiichi Sankyo, Bristol-Myers Squibb, and AstraZeneca. Saito has received grants from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, and ONO Pharmaceutical, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, ONO Pharmaceutical, and Pfizer. Reinmuth has received consulting fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, and Pfizer; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, and Takeda; received support for attending meetings and/or travel from Janssen, Sanofi, and Takeda; and participated on a data safety monitoring board or advisory board for Symphogen. Lowery, Mann, Stewart, and Jiang are employees of, and own stocks in, AstraZeneca. Garon has received grants paid to their institution from ABL-Bio, AstraZeneca, Bristol-Myers Squibb, Daiichi Sanko, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Gilead, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon, and Novartis; consulting fees paid to their institution from AbbVie, ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio, and Zymeworks; and support for attending meetings and/or travel from A2 Bio and Novartis. Mok reports receiving grants paid to their institution from AstraZeneca, Bristol-Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, and Xcovery; consulting fees from AbbVie Inc., ACEA Pharma, Adagene, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., AVEO Pharmaceuticals, Inc., Bayer Healthcare Pharmaceuticals Ltd., BeiGene, Berry Oncology, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol-Myers Squibb, Bowtie Life Insurance Company Limited, Bridge Biotherapeutics Inc., Covidien LP, C4 Therapeutics Inc., Cirina Ltd., CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Da Volterra, Daiichi Sankyo, Eisai, Elevation Oncology, F. Hoffmann-La Roche Ltd./Genentech, Fishawack Facilitate Ltd., G1 Therapeutics Inc., geneDecode Co., Ltd., Gilead Sciences, Inc., GLG’s Healthcare, Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Illumina Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lakeshore Biotech Ltd., Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/WebMD, Medtronic, Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES, MoreHealth, Novartis, Novocure GmbH, Omega Therapeutics Inc., OrigiMed, OSE Immunotherapeutics, PeerVoice, Pfizer, PrIME Oncology, Prenetics, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Regeneron Pharmaceuticals Inc., Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Simcere of America Inc., Synergy Research, Summit Therapeutics Sub, Inc., Takeda Pharmaceuticals HK Ltd., Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc., and Yuhan Corporation; receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ACEA Pharma, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., AstraZeneca (before January 1, 2019), BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communications, Janssen Pharmaceutica NV, Jiahui Holdings Co. Ltd., LiangYiHui Healthcare, Lilly, Lucence Health Inc., MD Health Brazil, Medscape LLC, Merck Pharmaceuticals HK Ltd., Merck Sharp & Dohme, MiRXES, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians’ Education Resource, Pfizer, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co. Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Oncology, and Touch Independent Medical Education Ltd.; receiving support for attending meetings and/or travel from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme (paid to institution), Novartis, Roche (paid to self and institution), AstraZeneca, Daiichi Sankyo, MiRXES, AbbVie, Zai Lab, and Liangyihui (paid to self); having participation on a data safety monitoring board or advisory board for AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim, Bowtie Life Insurance Co., Ltd., Bristol-Myers Squibb, C4 Therapeutics Inc., Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Daiichi Sankyo Inc., Eisai, Fishawack Facilitate Ltd., G1 Therapeutics Inc., Gilead Sciences Inc., Gritstone Oncology Inc., Guardant Health, geneDecode Co. Ltd. (uncompensated), Hengrui Therapeutics Inc., HutchMed, Ignyta Inc., Incyte Corporation, Imagene AI Ltd., Inivata, IQVIA, Janssen, Lakeshore Biotech, Lilly, Loxo-Oncology Inc., Lunit Inc., Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Roche/Genentech, Regeneron Pharmaceuticals Inc., Sanofi-Aventis R&D, SFJ Pharmaceutical, Simcere of America Inc., Simcere Zaiming, Inc., Takeda, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc., and Yuhan Corporation; having leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with AstraZeneca PLC, HutchMed, and Aurora; and having stock or stock options in AstraZeneca, Aurora Tele-Oncology Ltd., Biolidics Ltd., HutchMed, Prenetics, D3 Bio, Lunit, Bowtie Life Insurance, Lakeshore Biotech Ltd., Loxo-oncology, Virtus Medical Group, and Phanes Therapeutics, Inc. Johnson has received research funding paid to their institution from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Carisma Therapeutics, Corvus Pharmaceutical, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo-Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, Y-mAbs Therapeutics, Bristol-Myers Squibb, Checkpoint Therapeutics, City of Hope National Medical Center, Jounce Therapeutics, Mythic Therapeutics, RasCal Therapeutics, WindMIL Therapeutics, ArriVent BioPharma, Bayer, LockBody Therapeutics, and Taiho Oncology; and receiving consulting fees paid to their institution from AbbVie, Amgen, Arrivent, Alentis Therapeutics, AstraZeneca, Bristol-Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Hookipa Biotech, Janssen, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Pyramid Biosciences, Revolution Medicines, Sanofi-Aventis, SeaGen, Takeda Pharmaceuticals, VBL Therapeutics, Arcus Biosciences, Immunocore, Jazz Pharmaceuticals, Synthekine, Boehringer Ingelheim, Gilead Sciences, Normunity, Lilly, Novocure, and Pfizer. The remaining authors delcare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy., Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded., Results: A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group., Conclusions: Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB)., Experimental Design: Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model., Results: The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672)., Conclusions: OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset. See related commentary by Rolfo and Russo, p. 652., (©2023 The Authors; Published by the American Association for Cancer Research.)

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT. Clinical Trial Registration : NCT05221840 (ClinicalTrials.gov).

Background: The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age., Patients and Methods: Patients were randomized 2:1 (1-42 days post-CRT) to receive 12-months' durvalumab (10 mg/kg intravenously every-2-weeks) or placebo. We analyzed PFS and OS (unstratified Cox-proportional-hazards models), safety and patient-reported outcomes (PROs: symptoms, functioning, and global-health-status/quality-of-life) in subgroups defined by a post-hoc 70-year age threshold. Data cut-off for PFS was February 13, 2017 and for OS, safety and PROs was March 22, 2018., Results: Overall, 158 of 713 (22.2%) and 555 of 713 (77.8%) randomized patients were aged ≥70 and <70 years, respectively. Durvalumab improved PFS and OS among patients aged ≥70 (PFS: hazard ratio [HR], 0.62 [95% CI, 0.41-0.95]; OS: HR, 0.78 [95% CI, 0.50-1.22]) and <70 (PFS: HR, 0.53 [95% CI, 0.42-0.67]; OS: HR, 0.66 [95% CI, 0.51-0.87]), although the estimated HR-95% CI for OS crossed one among patients aged ≥70. Durvalumab exhibited a manageable safety profile and did not detrimentally affect PROs vs. placebo, regardless of age; grade 3/4 (41.6% vs. 25.5%) and serious adverse events (42.6% vs. 25.5%) were more common with durvalumab vs. placebo among patients aged ≥70., Conclusion: Durvalumab was associated with treatment benefit, manageable safety, and no detrimental impact on PROs, irrespective of age, suggesting that elderly patients with unresectable, stage III NSCLC benefit from treatment with consolidation durvalumab after CRT. However, small subgroup sizes and imbalances in baseline factors prevent robust conclusions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ISEL (Iressa Survival Evaluation in Lung Cancer) clinical trial evaluated the efficacy of gefitinib versus placebo in pretreated nonsmall-cell lung cancer patients. Two different antibodies, scoring systems, and cutoff points of epidermal growth factor receptor (EGFR) protein expression were compared to predict response and survival of enrolled patients., Methods: EGFR expression was assessed in tumor samples by immunohistochemistry using the Dako EGFR pharmDx kit (scoring percent of tumor cells with positive staining) and Zymed monoclonal antibody clone 31G7 (scoring staining index derived from proportion of positive cells times staining intensity)., Results: Data for EGFR expression were available for 379 patients for Dako and 357 patients for Zymed antibody (22% and 21%, respectively, of trial population). Objective response rates in gefitinib-treated EGFR-positive patients defined with various cutpoints with Dako antibody varied between 8% and 12%, and with Zymed antibody between 10% and 13%. Lower cutoff points with Dako antibody provided the best discrimination between EGFR-positive and EGFR-negative patients for survival hazard ratios comparing gefitinib to placebo, with a significant treatment/cutoff point interaction for 10% cutoff point (P = .049). A similar but less apparent trend was noted for Zymed antibody, although the discrimination between hazard ratios was not significant for any cutoff point analyzed., Conclusions: Assessment with the Dako PharmDx kit and percentage of cells with positive staining may provide more accurate prediction of differential effect on survival with gefitinib than assessment with Zymed antibody and staining index. Using higher cutpoints to define positivity does not improve test discrimination.