Safety and Efficacy Outcomes of Early Cessation of Anti-PD1 Therapy in Patients 80 Years or Older: A Retrospective Cohort Study.

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (<12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n=286), non-small cell lung cancer (NSCLC) (n=345), urothelial cell carcinoma (UCC) (n=108), and renal cell carcinoma (RCC) (n=34). Of these, 102 met the primary endpoint of <12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.

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Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessio Cortellini declares grants for consultancies/advisory boards from MSD, OncoC4, IQVIA, AstraZeneca, Access Infinity, Ardelis-Health, Alpha Sight, Roche, REGENERON; speaker fees from AstraZeneca, Eisai, Pierre-Fabre, MSD, Sanofi/REGENERON; writing/editorial activity from BMS, MSD; travel support from Sanofi, MSD. Anwaar Saaed reports research grants (to institution) from AstraZeneca, Bristol Myers Squibb, Merck, Clovis, Exelixis, Actuate therapeutics, Incyte Corporation, Daiichi Sankyo, Five prime therapeutics, Amgen, Innovent biologics, Dragonfly therapeutics, Oxford biotherapeutics, KAHR medical, Biontech, and advisory board/consulting fees from AstraZeneca, Bristol Myers Squibb, Merck, Xilio therapeutics, Arcus therapeutics, Exelixis, Pfizer, and Daiichi Sankyo. Akiva Diamond served on an Advisory Board for Incyte. Christopher Hoimes has served on advisory boards or as a consultant for BMS, Merck, Seagen. Amin H. Nassar receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology and received consulting fees from Guidepoint Global. Dwight Owen discloses research funding (to institution) from BMS, Merck, Genentech, Palobiofarma, and Onc.AI. Toni Choueiri reports institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or honoraria past 5 years, ongoing or not, from: Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO and others), outside the submitted work. TC also reports institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA; equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium; committees: NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, KidneyCan; medical writing and editorial assistance support may have been funded by Communications companies in part; no speaker’s bureau. TC entored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. The institution of TC (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. David J Pinato declares the following competing interests: Lecture fees: Bayer Healthcare, Astra Zeneca, EISAI, Bristol Myers-Squibb, Roche, Ipsen; Travel expenses: Bristol Myers-Squibb, Roche, Bayer Healthcare; Consulting fees: Mina Therapeutics, Boeringer Ingelheim, Ewopharma, EISAI, Ipsen, Roche, H3B, Astra Zeneca, DaVolterra, Mursla, Starpharma, Avammune Therapeutics, LiFT Biosciences, Exact Sciences; Research funding (to institution): MSD, BMS, GSK. Thomas Marron currently or has previously served on Advisory and/or Data Safety Monitoring Boards for Rockefeller University, Regeneron, AbbVie, Merck, Bristol-Meyers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Celldex, Chimeric, DrenBio, Glenmark, Simcere, Surface, G1 Therapeutics, NGMbio, DBV Technologies, Arcus, Fate, Ono, Larkspur, and Astellas. Abdul Rafeh Naqash receives funding for trials he is PI on: Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, and NGM Biopharmaceuticals. ARN also received Consultant Editor Compensation from JCO Precision Oncology, Travel Compensation from: SITC/ AACR/ Conquer Cancer Foundation/BinayTara Foundation and Foundation Med, Caris Life Sciences, and serves on the Advisory Board for Foundation Med. Douglas Johnson has served on advisory boards or as a consultant for BMS, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte.