Abstract 635P
Background
Amivantamab plus carboplatin-pemetrexed (ami-chemo) is approved for the first-line (1L) treatment of advanced non-small cell lung cancer with EGFR Exon 20 insertions (PAPILLON study; Zhou NEJM 2023). There was a favorable trend in the intention-to-treat (ITT) interim analysis for overall survival (OS) in the ami-chemo arm with a hazard ratio (HR) of 0.67 (95% confidence interval [CI], 0.42–1.09) vs chemo, despite 42% (65/155) of patients in the chemo arm switching to receive second line (2L) ami monotherapy after disease progression. However, 2L ami might be unavailable in some clinical settings, and the ITT-based analysis may underestimate the benefit of 1L ami-chemo.
Methods
Kaplan-Meier survival estimates, estimating OS for the chemo arm in the absence of 2L ami, as well as corresponding OS HRs were generated using recommended statistical methods, including inverse probability of censoring weighting (IPCW), two-stage estimation (TSE), and rank-preserving structural failure time (RPSFT) modeling. A range of sensitivity analyses for each of the methods were conducted (e.g., adjusting for additional patients receiving 2L ami off-protocol or varying other statistical modeling assumptions).
Results
After adjusting for the effect of 2L ami in the chemo arm, OS HRs (95% CI) from IPCW, TSE, and RPSFT methods were 0.52 (0.28–0.94), 0.55 (0.31–0.92), and 0.60 (0.32–1.12), respectively. In the ITT analysis, at a median follow-up of 14.9 months, 80% and 72% of patients from the ami-chemo and chemo arms were alive, respectively. Corresponding survival estimates for the chemo arm using IPCW, TSE and RPSFT methods were 58%, 65% and 70%. Results remained generally consistent across sensitivity analyses, and these adjusted OS estimates for 1L chemo are aligned with previously published estimates using real world evidence.
Conclusions
After adjusting for cross-over, estimates of OS benefit were in favor of ami-chemo vs chemo across multiple methodologies and statistical assumptions, providing a more clinically relevant estimate of benefit for ami-chemo vs chemo in 1L.
Clinical trial identification
NCT04538664.
Editorial acknowledgement
Medical writing assistance was provided by Suparna Abraham, PharmD, of Lumanity Communications Inc.
Legal entity responsible for the study
Janssen Research & Development.
Funding
Janssen Global Services LLC.
Disclosure
S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Zai Lab, GenomiCare, Yuhan, Roche, Menarini, InventisBio Co. Ltd; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh Pharma, Hengrui Therapeutics; Financial Interests, Personal, Research Funding: AstraZeneca, Hutchison MediPharma, Bristol Myers Squibb, Hengrui Therapeutics, BeiGene, Roche, Hansoh, Lilly Suzhou Pharmaceutical Co. C. Zhou: Financial Interests, Personal, Invited Speaker, speaking fee, advisory role: Eli Lily; Financial Interests, Personal, Invited Speaker, honoraria as a speaker: Roche, Sanofi, Boehringer Ingelheim, MSD, C-Stone; Financial Interests, Personal, Invited Speaker, Speaking fee, advisory role: Qilu Pharma; Financial Interests, Personal, Invited Speaker, honoraria as a speaker, advisor: Hengrui, Innovent Biologics, TopAlliance Biosciences Inc; Financial Interests, Personal, Invited Speaker, honoraria as a speaker: LUYE Pharma; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnositics; Financial Interests, Personal, Other, honoraria as a speaker: Alice; Financial Interests, Personal, Other, honoraria as a speaker from AnHeart: AnHeart. B.C. Cho: Financial Interests, Personal, Other, Consulting 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, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, 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, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, 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, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. A. Ono: Financial Interests, Institutional, Local PI: AstraZeneca, Janssen Research & Development, Chugai. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd., Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services JAPAN K.K, SYNEOS HEALTH CLINICAL K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co., Ltd,., Covance Japan Inc., EP-CRSU CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co., Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co., Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Personal, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, BMS, SANOFI; Financial Interests, Personal, Invited Speaker: AMGEN, ROCHE, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche; Non-Financial Interests, Personal, Leadership Role, Board Member: Associacio contra el Cancer Barcelona. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Pfizer, Eli Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Merck (German), Novartis, Abion, Abion, Beigene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. G. Richardson: Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Roche, Genentech, Shanghai Fosun Pharmaceutical Development Company; Financial Interests, Institutional, Local PI: AstraZenica, Merck, Takeda, BeiGene, Pfizer, CBT Pharmaceuticals, Corvus Pharmaceuticals, Novotech, Shanghai Henlius Biotech Inc, Five Prime Therapeutics Inc, Suzhou Alphamab Co, Boehringer Ingelheim, Adagene Inc, Bio-Thera Solutions, ChemoCentryx, Curon Biopharmaceutical, D3io Co Ltd, Inventis Bio, Senz Oncology Pty Ltd, Genfleet Therapeutics, GeneQuantum Healthcare Co Ltd, Keythera Pharmaceuticals Pty Ltd, LaNova Australia Pty Ltd, Medicenna Therapeutics Inc, Minghui Pharmaceutical, Neoleukin Therapeutics, PharmAbcine Australia Pty Ltd, Remegen, Seattle Genetics, Surface Oncology, Eucure Biopharma, Janssen Oncology, ImmunGen Inc, Imugene Ltd, Therapim, Agenus. J.K. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regenero, Sanofi Genzyme, Takeda, Mirati Therapeutics. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serona, Daiichi Sankyo, Lilly Oncology, Janssen, Macroger, Sanofi, Avero, Regenero, Mirati Therapeutics, GSK, G1 Therapeutics, ; Financial Interests, Personal, Invited Speaker: Illumina; Financial Interests, Personal, Steering Committee Member: GSK, Janssen; Financial Interests, Institutional, Funding: Merck, AstraZeneca, Jounce; Financial Interests, Institutional, Other: BMS. A.S. Mansfield: Financial Interests, Institutional, Research Grant: Novartis, Verily; Financial Interests, Institutional, Speaker, Consultant, Advisor: Rising Tide, TRIPTYCH Health Partners Expert Think Tank; Financial Interests, Institutional, Speaker’s Bureau: Janssen, BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Ideology Health LLC (formerly Nexus Health Media), AXIS Medical Education, Inc., Johnson & Johnson Global Services, Intellisphere LLC (OncLive Summit Series), Answers in CME, Immunocore ; Financial Interests, Personal, Speaker’s Bureau: Antoni van Leeuwenhoek Kanker Instituut, University of Miami Int’l Mesothelioma Symposium; Financial Interests, Personal, Other, Travel: Shanghai Roche; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Takeda Oncology; Financial Interests, Personal, Other, Non-remunerated Director: Mesothelioma Applied Research Foundation, Friends of Patan Hospital; Financial Interests, Personal, Research Funding: Bristol Myers Squibb. N. Buyukkaramikli, N. Perualila, C. Chandler, L. Dearden, T. Agrawal, M. Baig: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. S. Acharya: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Other, Stocks: Janssen. K. Park: Financial Interests, Personal, Advisory Board: JNJ, AstraZeneca, Daiichi Sankyo, Eli Lilly, Samsung Medical Center; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, DMC member: BeiGene, Incyte; Financial Interests, Personal, Other, Advisor/Consultant: Genius, IMBdx; Financial Interests, Personal, Other, Advisor: ABION; Financial Interests, Personal, Stocks/Shares, Stock option: IMBDx, Genius.