Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer

Abstract

IMPORTANCE Geriatric (aged Ն80 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 Ն80 years) with cancer. DESIGN, SETTING, AND PARTICIPANTSA 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 MEASURESClinical 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 Ն85 years). Among all 928 patients, 383 (41.3%) experienced Ն1 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 RELEVANCEThe 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.

Phase 2 study of first‐line pembrolizumab monotherapy in elderly patients with non‐small‐cell lung cancer expressing high PD‐L1

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Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer

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Study shows that patients older than 80 years benefit from immunotherapy

“…The study was reported in JAMA Oncology. 1 In this study, researchers retrospectively analyzed the outcomes of 928 patients at 18 academic medical centers across the United States and Europe who had cancer, were aged 80 years or older, and were treated with single-agent ICIs. The researchers primarily reviewed 3 types of cancer: non-small cell lung cancer; melanoma; and genitourinary tumors, including prostate, bladder, and kidney cancer.…”

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