Impact of concomitant co-medications on survival with first-line pembrolizumab in 43,000 French patients with advanced NSCLC

BackgroundAntibiotics (ATB), steroids (STD) and proton pump inhibitors (PPI) are suspected to interact with the efficacy of pembrolizumab. ATHENA is a study using a comprehensive claim database that aimed at exploring the link between co-medications and overall survival (OS) in patients (pts) with advanced non-small-cell lung cancer (NSCLC).MethodsUsing the French National Health Insurance database (SNDS), we identified pts newly diagnosed with lung cancer in France from 2015 to 2022. Treatments and pts characteristics were extracted or inferred from hospital, outpatient care and pharmacy delivery reports. Concomitant co-medication was defined as having at least 2 intakes of PPI/STD/ATB within one month before or after the start of pembrolizumab. Hazard ratio (HR) were estimated with Cox model and using inverse probability therapy weighting (IPTW) to adjust for several confounders, such as comorbidities and socio-economic status. A one-month landmark was applied to account for immortal-time bias.Results391,106 pts with lung cancer were identified, with 50,083 receiving pembrolizumab for an advanced disease, 43,359 (86.6%) in first line, alone or with chemotherapy. 67.0% were male, with a median age of 65 [58-71], and 31.7% of pts were older than 70 years old. 61.3% received pembrolizumab plus chemotherapy. PD-L1 was not available. After a median follow-up of 25.9 mo CI95%[25.6-26.2], the median OS after pembrolizumab initiation was 15.7 mo [15.3-16.0]. Among the 43,359 pts treated by up-front pembrolizumab, at treatment initiation, 26.0% pts were exposed to ATB, 55.6% to STD and 45.2% to PPI. ATB and STD exposures were not associated with OS, HR=1.02 [0.99-1.05] p=0.24 and HR=0.98 [0.95-1.02] p=0.28 respectively. PPI exposure was associated with worse OS HR=1.09 [1.06-1.13] p<0.001.ConclusionsThis study, using a comprehensive French database encompassing all patients with incident lung cancer treated with pembrolizumab between 2015 and 2022, supports the safety of co-medications with STD and ATB, and suggests that PPI exposure is associated with worse OS.Legal entity responsible for the studyGustave Roussy.FundingHas not received any funding.DisclosureS. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd., Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. J. Remon Masip: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Merck, TAKEDA; Financial Interests, Personal, Other, Travel, accommodation: OSE Immunotherapeutics; Financial Interests, Institutional, Advisory Board: EDI Mack; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. P. Lavaud: Financial Interests, Other: Janssen, AstraZeneca, Sanofi, MSD, Sandoz; Financial Interests, Institutional, Funding: Service. M. Aldea: Financial Interests, Other: Sandoz, Viatris; Financial Interests, Institutional, Funding: Amgen, AstraZeneca. M. Frelaut: Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Coordinating PI: Ipsen; Non-Financial Interests, Advisory Role: SOFOG, EORTC, INCA; Non-Financial Interests, Member: EORTC, ASCO, SOFOG. C. Le Pechoux: Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche, BMS, Roche, Varian; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Other, Travel: Janssen; Other, travel: Ose Immunotherapeutics. A. Levy: Financial Interests, Institutional, Invited Speaker: Pharma Mar; Financial Interests, Institutional, Funding: AstraZeneca, Roche; Financial Interests, Institutional, Coordinating PI: BeiGene. A. Gazzah: Financial Interests, Other: Boehringer Ingelheim, Novartis, Pfizer, Roche, Sanofi; Financial Interests, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BeiGene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd., 4D Pharma, AbbVie, Da Voltera, Eli Lilly, Ellipse pharma Ltd., F-Star, GSK, Janssen, Onxeo, OSE Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD; Financial Interests, Institutional, Local PI: AbbVie, Amgen, Blueprint Medicines, Daiichi Sankyo, Pfizer, Roche-Genentech, Turning Point Therapeutics, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, OSE Immunotherapeutics, Sanofi, Taiho; Financial Interests, Institutional, Steering Committee Member: BeiGene, GSK, Janssen, Takeda, Genmab; Financial Interests, Institutional, Funding: Cristal Therapeutics. All other authors have declared no conflicts of interest.