Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer
Authors: Caroline A. Nebhan, Alessio Cortellini, Weijie Ma, Teja Ganta, Haocan Song, Fei Ye, Rebecca Irlmeier, Neha Debnath, Anwaar Saeed, Maluki Radford, Asrar Alahmadi, Akiva Diamond, Christopher Hoimes, Nikhil Ramaiya, Carolyn J. Presley, Dwight H. Owen, Sarah Abou Alaiwi, Amin Nassar, Biagio Ricciuti, Giuseppe Lamberti, Melissa Bersanelli, Chiara Casartelli, Sebastiano Buti, Paolo Marchetti, Raffaele Giusti, Marco Filetti, Vito Vanella, Domenico Mallardo, Shravanti Macherla, Tamara A. Sussman, Andrea Botticelli, Domenico Galetta, Annamaria Catino, Pamela Pizzutilo, Carlo Genova, Maria Giovanna Dal Bello, Foteini Kalofonou, Ella Daniels, Paolo A. Ascierto, David J. Pinato, Toni K. Choueiri, Douglas B. Johnson, Thomas U. Marron, Yinghong Wang, Abdul Rafeh Naqash
Journal: JAMA Oncology (2021)

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.To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged ≥80 years) with cancer.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.Clinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs.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).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.