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Multicenter Study
. 2021 Dec 1;7(12):1856-1861.
doi: 10.1001/jamaoncol.2021.4960.

Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer: A Multicenter International Cohort Study

Caroline A Nebhan  1 , Alessio Cortellini  2   3 , Weijie Ma  4   5 , Teja Ganta  6 , Haocan Song  7 , Fei Ye  7 , Rebecca Irlmeier  7 , Neha Debnath  6 , Anwaar Saeed  8 , Maluki Radford  8 , Asrar Alahmadi  9   10 , Akiva Diamond  9   11 , Christopher Hoimes  9   12 , Nikhil Ramaiya  9 , Carolyn J Presley  13 , Dwight H Owen  13 , Sarah Abou Alaiwi  14 , Amin Nassar  14 , Biagio Ricciuti  15 , Giuseppe Lamberti  16 , Melissa Bersanelli  17 , Chiara Casartelli  17 , Sebastiano Buti  17 , Paolo Marchetti  18 , Raffaele Giusti  18 , Marco Filetti  18 , Vito Vanella  19 , Domenico Mallardo  19 , Shravanti Macherla  20 , Tamara A Sussman  21 , Andrea Botticelli  22 , Domenico Galetta  23 , Annamaria Catino  23 , Pamela Pizzutilo  23 , Carlo Genova  24   25 , Maria Giovanna Dal Bello  24 , Foteini Kalofonou  3 , Ella Daniels  3 , Paolo A Ascierto  19 , David J Pinato  3   26 , Toni K Choueiri  14 , Douglas B Johnson  1 , Thomas U Marron  6 , Yinghong Wang  4 , Abdul Rafeh Naqash  20   27   28
Affiliations
Multicenter Study

Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer: A Multicenter International Cohort Study

Caroline A Nebhan et al. JAMA Oncol. .

Abstract

Importance: Geriatric (aged ≥80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population.

Objective: To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged ≥80 years) with cancer.

Design, setting, and participants: A Multicenter, international retrospective study of 928 geriatric patients with different tumors treated with single-agent ICIs between 2010 to 2019 from 18 academic centers in the US and Europe. Analyses were conducted from January 2021 to April 2021.

Main outcomes and measures: Clinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs.

Results: Median (range) age of the 928 patients at ICI initiation was 83.0 (75.8-97.0) years. Most patients (806 [86.9%]) were treated with anti-programmed cell death 1 therapy. Among the full cohort, the 3 most common tumors were non-small cell lung cancer (NSCLC, 345 [37.2%]), melanoma (329 [35.5%]), and genitourinary (GU) tumors (153 [16.5%]). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median PFS and OS, respectively, were 6.7 and 10.9 months (NSCLC), 11.1 and 30.0 months (melanoma), and 6.0 and 15.0 months (GU). Within histologically specific subgroups (NSCLC, melanoma, and GU), clinical outcomes were similar across age subgroups (aged <85 vs ≥85 years). Among all 928 patients, 383 (41.3%) experienced ≥1 irAE(s), including 113 (12.2%) that were reported to be grade (G) 3 to 4 based on Common Terminology Criteria for Adverse Events (version 5.0). The median time to irAE onset was 9.8 weeks; 219 (57%) occurred within the first 3 months after ICI initiation. Discontinuation of treatment with ICIs owing to irAEs occurred in 137 (16.1%) patients. There was no significant difference in the rate of irAEs among patients aged younger than 85, 85 to 89, and 90 years or older. Despite the similar rate of G3 or higher irAEs, ICIs were discontinued due to irAEs more than twice as often among patients aged 90 years or older compared with patients younger than 90 years (30.9% vs 15.1%, P = .008).

Conclusions and relevance: The findings of this international cohort study suggest that treatment with ICIs may be effective and generally well tolerated among older patients with cancer, though ICI discontinuation owing to irAEs was more frequent with increasing age.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cortellini receives grant consultancies/speaking fees from MSD, BMS, AstraZeneca, Novartis, Astellas, SunPharma and Roche. Dr Saeed receives research funding (to institution) from Merck, Bristol Myers Squibb (BMS), AstraZeneca, Exelixis, Clovis, and Daiichi Sankyo, and also serves on advisory boards for Merck, BMS, AstraZeneca, Pfizer, Exelixis, and Daiichi Sankyo. Dr Owen receives research funding (to institution) from BMS, Merck, PaloBiofarma, and Genentech. Dr Owen reports clinical consulting for theMednet.org. Dr Giusti has/had a consultant/advisory role for Roche-Genentech, AstraZeneca, Takeda, Boehringer Ingelheim. Travel support from Boehringer Ingelheim. Dr Bersanelli received honoraria as a speaker at scientific events by BMS, Novartis, AstraZeneca, and Pfizer and as a consultant for advisory role by Novartis, BMS, and Pfizer; she also received fees for copyright transfer by Sciclone Pharmaceuticals and research funding by Seqirus UK, Pfizer, Novartis, BMS, AstraZeneca, Roche S.p.A., and Sanofi Genzyme. Dr Buti received honoraria as a speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. Dr Genova receives honoraria from AstraZeneca, BMS, Merck Sharp & Dohme, Boehringer Ingelheim, and Roche. Dr Ascierto has/had a consultant/advisory role for BMS, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Takis, Lunaphore. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Array, Sanofi and travel support from MSD. Dr Pinato received lecture fees from ViiV Healthcare, Roche, Eisai, Bayer Healthcare, Falk Foundation; travel expenses from BMS, MSD, Roche, and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, AstraZeneca, H3B, DaVolterra; received research funding (to institution) from MSD, BMS. Dr Choueiri has served on advisory boards, consultant and/or received honorarium from AstraZeneca, Aravive, Aveo, Bayer, BMS, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi Aventis, Takeda, Tempest, Up-To-Date, and CME events (Peerview, OncLive, and others). Dr Johnson serves on advisory boards for Array Biopharma, BMS, Catalyst, Iovance, Janssen, Merck, Novartis, and Oncosec, and receives research funding from BMS and Incyte. Dr Marron has served on advisory boards for Regeneron, Boehringer Ingelheim, AstraZeneca, Genentech, and Atara. He has research grants from Regeneron, Boehringer Ingelheim, Merck, and BMS. Dr Wang serves as consultant for Tillotts Pharma. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Progression-Free Survival (PFS) in Geriatric Patients Treated With Immune Checkpoint Inhibitors
Figure 2.
Figure 2.. Overall Survival (OS) of Geriatric Patients Treated With Immune Checkpoint Inhibitors
See this image and copyright information in PMC

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