LBA3 - Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in first-line metastatic (m) NSCLC: 5-year overall survival (OS) update from the POSEIDON study

Background

In the phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in both progression-free survival (PFS) and OS (HR 0.77; 95% CI 0.65‒0.92; p=0.0030; median follow-up [FU] 34.9 mo in censored patients [pts] across all three arms) vs CT alone in pts with EGFR/ALK wild-type mNSCLC, leading to approvals for this regimen. D+CT significantly improved PFS vs CT, with a trend for OS improvement that did not reach statistical significance (HR 0.86; 95% CI 0.72‒1.02; p=0.0758). Here we report long-term OS results after median FU of >5 y.

Methods

Pts (n=1013) were randomised 1:1:1 to 1L treatment with: D (until progression) ± limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles); or CT (up to 6 cycles). Stratification factors were tumour cell (TC) PD-L1 expression (TC ≥50% vs <50%; VENTANA PD-L1 [SP263] assay), disease stage (IVA vs IVB) and histology (squamous vs NSQ). Long-term FU analysis of OS was prespecified. Serious AEs were collected during long-term FU.

Results

T+D+CT showed sustained OS benefit vs CT (HR 0.76; 95% CI 0.64–0.89) at an updated data cutoff of 24 Aug 2023 (median FU 63.4 mo in censored pts), with 5-y OS rates of 15.7% vs 6.8% (Table). OS improvement with D+CT vs CT remained lower in magnitude (HR 0.84; 95% CI 0.72–1.00; 5-y OS 13.0%). Updated results suggested that OS benefit with T+D+CT vs CT continued to be more pronounced in pts with NSQ vs squamous histology (data will be presented). Consistent with earlier analyses, OS benefit was maintained with T+D+CT (but not D+CT) vs CT in pts with PD-L1 TC <1%. OS by STK11/KEAP1/KRAS mutation status will be presented. No new safety signals were identified. Table: LBA3

*Stratified/^†unstratified analysis. mOS, median OS; NSQ, non-squamous.

Conclusions

Updated analyses from POSEIDON after median FU of >5 y showed durable long-term OS benefit with the approved regimen of T+D+CT (vs CT alone). These results support its use as a 1L treatment option for pts with mNSCLC, including harder-to-treat subgroups such as those with PD-L1 TC <1%.

Clinical trial identification

NCT03164616, 23 May 2017.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

S. Peters: Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Advisory Board: 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-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Novocure, OncologyEducation, Pharma Mar, Promontory Therapeutics, PER, Peerview, Pfizer, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; Financial Interests, Institutional, Member of Board of Directors: Galenica; Financial Interests, Institutional, Principal Investigator: Amgen, Arcus, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech, Seattle Genetics; Non-Financial Interests, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Non-Financial Interests, Personal, Advisory Role: Cf. advisory boards; Non-Financial Interests, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP scientific chair. B.C. Cho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Guardant, Roche, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gliead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS Bio; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS Bio; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Personal, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center, Vertical Bio AG; Financial Interests, Personal, Advisory Role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi; Non-Financial Interests, Personal, Other, Founder: Daan Biotherapeutics. 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Laktionov: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad, Pfizer; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche AG, Biocad. M. Hussein: Financial Interests, Personal, Advisory Role: IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis, Biopahrama, Oncocyte, Aptitude Health, National Community Oncology Dispensing Association, Integra PrescisionQ, AbbVie, CTI BioPharma C. C.T. Yang: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Gilead Sciences, Novartis, Ono, Pfizer, Takeda; Non-Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Novartis, Ono, Pfizer, Takeda; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Gilead Sciences, Novartis, Ono, Pfizer, Takeda. H. Saito: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical; Financial Interests, Personal, Principal Investigator: AstraZeneca, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical. N. 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Hoffmann-La Roche Ltd., Genentech, GLG’s Healthcare, Fishawack Facilitate Ltd., G1 Therapeutics Inc., geneDecode Co., Ltd, Gilead Sciences, Inc. 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, MSD, 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., Summit Therapeutics Sub, Inc., Synergy Research, Takeda Pharmaceuticals HK Ltd., Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc., Yuhan Corporation; Non-Financial Interests, Personal, Leadership Role: American Society of Clinical Oncology (ASCO) (2018 – 2022); Asian Thoracic Oncology Research Group (ATORG) (2016 – Present); Chinese Lung Cancer Research Foundation Limited (CLCRF) (2005 – 2012), Chinese Society of Clinical Oncology (CSCO) (2009 – 2020); Hong Kong Cancer Fund (HKCF) (2011 - Present); Hong Kong Cancer Therapy Society (HKCTS) (2004 – Present), International Association for the Study of Lung Cancer (IASLC) (2007 – 2019); St. Stephen’s College & Prep. School (2017 – Present); Hong Kong Academy of Sciences (ASHK) (2022 – Present). M.L. Johnson: Financial Interests, Institutional, Research Grant: 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 Pharmaceuticals, 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, Tu, Y-mAbs Therapeutics, Bristol Myers Squibb, Checkpoint Therapeutics, City of Hope National Medical Center, Jounce Therapeutics, Mythic Therapeutics, RasCal Therapeutics, WindMIL Therapeutics, ArriVent BioPharma, LockBody Therapeutics, Taiho Oncology; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arrivent, Astellas, AstraZeneca, Calithera Biosciences, Daiichi Sankyo, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, 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, Bristol Myers Squibb, D3 Bio Limited, Fate Therapeutics, Gilead Sciences, Hookipa Biotech, Lilly, Normunity, Novocure, Pfizer. All other authors have declared no conflicts of interest.