In a multicenter international retrospective cohort study reported in JAMA Oncology, Caroline A. Nebhan, MD, PhD, of Vanderbilt University Medical Center, and colleagues found that single-agent immune checkpoint inhibitor therapy in patients with cancer aged 80 and older appeared to be effective and generally well tolerated.1
Caroline A. Nebhan, MD, PhD
As stated by the investigators: “Geriatric (aged ≥ 80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of … [immune checkpoint inhibitors] in geriatric patients. These agents are associated with immune-related adverse events…, which may be particularly associated with morbidity in this population.”
The study involved data from 928 geriatric patients with different tumors treated with single-agent immune checkpoint inhibitors between 2010 to 2019 at 18 centers in the United States and Europe. Median age at immune checkpoint inhibitor initiation was 83.0 years (range = 75.8–97.0 years), with 626 (67.5%) aged up to 85, 242 (26.1%) aged 85 to 89, and 60 (6.5%) aged 90 and older. Treatment consisted of PD-1 inhibitors in 806 (86.9%), PD-L1 inhibitors in 79 (8.5%), and CTLA-4 inhibitors in 43 (4.6%). The three most common tumor types were non–small cell lung cancer (NSCLC, n = 345, 37.2%), melanoma (n = 329, 35.5%), and genitourinary (GU) cancers, including urothelial cell carcinoma, renal cell carcinoma, and prostate cancer (n = 153, 16.5%). The remaining 101 patients (10.9%) had 18 different malignancies. Clinical outcomes were analyzed for NSCLC, melanoma, and GU cancers.
Among 276 response-evaluable patients with NSCLC, the objective response rate was 32.2% (complete response in 3.6%), with response rates of 34.5% vs 25.7% among patients aged < 85 vs ≥ 85 years (P = .18). Among all patients with NSCLC, median progression-free survival and median overall survival were 6.7 months (95% confidence interval [CI] = 5.2–8.6 months) and 10.9 months (95% CI = 8.6–13.1 months). For patients aged < 85 vs ≥ 85 years, median progression-free survival was 8.0 months vs 5.0 months (P = .40), and median overall survival was 11.8 vs 7.5 months (P = .047).
Among 280 response-evaluable patients with melanoma, the objective response rate was 39.3% (complete response in 18.2%), with response rates of 35.8% vs 45.5% among patients aged < 85 years vs ≥ 85 years (P = .11). Among all patients with melanoma, median progression-free and overall survival were 11.1 months (95% CI = 8.9–16.0 months) and 30.0 months (95% CI = 23.6–46.4 months). For patients aged < 85 vs ≥ 85 years, median progression-free survival was 13.6 vs 7.4 months (P = .23), and median overall survival was 34.2 vs 24.5 months (P = .30).
Among 126 response-evaluable patients with GU cancers, the objective response rate was 26.2% (complete response in 4.0%), with response rates of 29.8% vs 19.0% among patients aged < 85 vs ≥ 85 years (P = .20). Among all patients with GU cancers, median progression-free survival and overall survival were 6.0 months (95% CI = 5.0–10.7 months) and 15.0 months (95% CI = 9.1–25.4 months). For patients aged < 85 vs ≥ 85 years, median progression-free survival was 6.5 vs 6.0 months (P = .25), and median overall survival was 15.7 vs 7.2 months (P = .13).
In an analysis adjusting for sex, stage, prior therapy, and Eastern Cooperative Oncology Group performance status, increasing age was not significantly associated with progression-free or overall survival in the NSCLC, melanoma, or GU cancer cohorts.
Immune-Related Adverse Events
A total of 383 patients (41.3%) had at least one immune-related adverse event, with grade 3 or 4 events occurring in 113 (12.2%); no deaths due to immune-related adverse events were observed. Median time to adverse event onset was 9.8 weeks, with 219 of the 383 patients (57.2%) experiencing events within the first 3 months after starting immune checkpoint inhibitor treatment. There was no significant difference in the rate of adverse events among patients aged < 85 years (43.1%, 12.9% grade 3 or 4), 85 to 89 years (37.2%, 10.3% grade 3 or 4), or ≥ 90 years (38.3%, 11.7% grade 3 or 4). The most common specific immune-related adverse events of any grade among all patients were dermatitis (14.2%; 15.2%, 11.2%, and 15.0% in < 85, 85–89, and ≥ 90 year groups), colitis/diarrhea (9.2%; 9.6%, 8.7%, and 6.7%), thyroid events (8.1%; 9.3%, 5.4%, and 6.7%), and pneumonitis (5.2%; 6.1%, 2.9%, and 5.0%). Among grade 3 or 4 events, the most common among all patients included colitis/diarrhea (3.6%), dermatitis (2.8%), hepatitis (2.6%), and pneumonitis (2.2%).
In patients with NSCLC, melanoma, and GU cancers, objective response rates were 32.2%, 39.3%, and 26.2%, respectively, and median overall survival was 10.9, 30.0, and 15.0 months.
Immune-related adverse events occurred in 41.3% of patients and were grade 3 to 4 in 12.2%; adverse events led to treatment discontinuation in 16.1% of patients.
Discontinuation of immune checkpoint inhibitor treatment due to immune-related adverse events occurred in 137 patients (16.1%); among those discontinuing treatment, 64 (46.7%) did so due to grade 3 or 4 events. Although the incidences of any-grade and grade 3 or 4 immune-related adverse events were similar among age groups, immune checkpoint inhibitor treatment was discontinued due to adverse events in 30.9% of patients aged ≥ 90 years vs 15.1% of younger patients (P = .008; 15.1% of those aged < 85, and 15.0% of those aged 85–89 years).
The investigators concluded: “The findings of this international cohort study suggest that treatment with [immune checkpoint inhibitors] may be effective and generally well tolerated among older patients with cancer, though [immune checkpoint inhibitor] discontinuation owing to [immune-related adverse events] was more frequent with increasing age. [The findings suggest] that age alone should not preclude patients from treatment with [immune checkpoint inhibitor].”
DISCLOSURE: The study was supported by the National Cancer Institute, National Institute on Aging, and others. For full disclosures of study authors, visit jamanetwork.com.
1. Nebhan CA, Cortellini A, Ma W, et al: 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. JAMA Oncol 7:1856-1861, 2021.
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