12MO - Patterns of response in metastatic (m) NSCLC after 2 and 4 cycles of chemotherapy (CT), alone or with durvalumab (D) ± tremelimumab (T), in the phase III POSEIDON study

Background

In POSEIDON, 1L T plus D and 4 cycles of platinum-based CT significantly improved PFS and OS vs CT in patients (pts) with EGFR/ALK wild-type mNSCLC leading to the approval of T+D+CT by the FDA; objective response rate (confirmed; 38.8% [95% CI, 33.6–44.3] and 41.5% [95% CI, 36.1–47.0] vs 24.4% [95% CI, 19.9–29.4]) and duration of response were also improved with both T+D+CT and D+CT vs CT. However, the relationship between number of CT cycles and patterns of response in pts with mNSCLC has not been fully established. Here we report outcomes in POSEIDON after 2 vs 4 CT cycles.

Methods

Pts (n = 1013) were randomised (1:1:1) to 1L T+D+CT, D+CT or CT. Exploratory analyses of objective response (intent-to-treat [ITT] population and subgroups with mutations [m] in STK11, KEAP1 or KRAS) and safety (safety population) were conducted after 2 vs 4 CT cycles (week 6 vs 12 scans, respectively).

Results

78%, 82% and 74% of pts who received T+D+CT, D+CT or CT completed 4 CT cycles. 560 pts had stable disease (SD) after cycle (C) 2. Of these, 22.9% had partial response (PR) after C4 (table). A similar trend was observed in pts with STK11m, KEAP1m or KRASm mNSCLC; in these pts, improvement appeared greatest with T+D+CT, although 95% CIs were wide and overlapping. Of 252 pts in the ITT with CR/PR after C2, 89.7% remained in response after C4 (table). Reductions in median target lesion size occurred between C2 and C4 in all arms (data will be presented). The frequency of grade 3/4 adverse events (AEs) and serious AEs originating in C1–2 and C3–4 was similar (data will be presented).

NSQ, non-squamous.

Conclusions

These exploratory data support the use of 4 CT cycles, when given with T (limited course) and D (until progression), to optimise response and tumour shrinkage in pts with mNSCLC, including some harder to treat subgroups. Two further CT cycles did not meaningfully add to toxicity or compromise the ability to administer planned CT.

Clinical trial identification

NCT03164616.

Editorial acknowledgement

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

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

N. Reinmuth: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Eli Lilly, Merck, MSD, Pfizer, Symphogen, Takeda; Financial Interests, Personal, Other, Consulting fee: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, Merck, MSD, Pfizer. B.C. Cho: 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, Advisory Role: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Invited Speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Other, Consultant: 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, Medpacto, Blueprint medicines, RandBio, Hanmi; 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 Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Financial Interests, Personal, Other, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen, Eli Lilly, Takeda, BMS, MSD, Pfizer, Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Janssen, Eli Lilly, Takeda, BMS, MSD, Pfizer, Amgen. S. Lucien Geater: Financial Interests, Personal, Full or part-time Employment: Prince of Songkla University; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche, Novartis, Samsung. S. Kim: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Novartis, Eli Lilly, Takeda, Therapex, and Yuhan; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Yuhan. M. Hussein: Financial Interests, Personal, Other, Honoraria: IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis, BioPharma, AbbVie, Oncocyte, Aptitude Health. L.H. Araujo: Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca, BMS; Financial Interests, Personal, Other, Honoraria; speaker: Eli Lilly, MSD, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck, Roche, Amgen; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim, MSD, Bristol Myers Squibb, Roche, Pfizer, AstraZeneca, Novartis, Merck. H. Saito: Financial Interests, Personal, Other, Honoraria: ONO Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: AstraZeneca, ONO Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical. K. Barrett: Financial Interests, Personal, Full or part-time Employment, Contractor: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Takeda. C. Lowery: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Tattersfield: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Role: AbbVie, ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon, and Novartis. T.S.K. Mok: Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Aurora Tele-Oncology Ltd., Biolidics Ltd., HutchMed, Prenetics; Financial Interests, Personal, Other, Stock option: Bowtie Life Insurance Co. Ltd., Lakeshore Biotech Ltd., Loxo-oncology, Lunit USA, Inc., Virtus Medical Group, D3 Bio; Financial Interests, Personal, Advisory Role: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, BerGenBio ASA, 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, Inivata, IQVIA, Janssen, Lakeshore Biotech, Eli Lilly, Loxo-Oncology Inc., Lunit, Inc., Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Roche/Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Simcere of America Inc., Takeda, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation; Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed, Aurora, 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); Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. LTD, LiangYiHui Healthcare, Eli 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., Shanghai Promedican Pharmaceuticals Co., Ltd., Taiho Pharmaceutical Co. Ltd, Takeda Oncology, Touch Independent Medical Education Ltd; Financial Interests, Personal, Other, Contractor: AbbVie Inc., ACEA Pharma, Adagene, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, 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. Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Eli Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHealth, Novartis, Omega Therapeutics Inc., OrigiMed, OSE Immunotherapeutics, PeerVoice, Pfizer, PrIME Oncology, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals/ Diagnostics/ Foundation One, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Simcere of America Inc., Synergy Research, Takeda Pharmaceuticals HK Ltd., Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery; Non-Financial Interests, Personal, Member of the Board of Directors: American Society of Clinical Oncology, Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO). M.L. Johnson: Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Ideaya Biosciences, iTeos, Janssen, Eli Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi-Aventis, SeaGen, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; 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, Eli 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. All other authors have declared no conflicts of interest.