In a multicenter international retrospective cohort study reported in JAMA Oncology, Nebhan et al found that single-agent immune checkpoint inhibitor therapy in patients with cancer aged ≥ 80 years appeared to be effective and generally well tolerated.

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.”

Study Details

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 < 85, 242 (26.1%) aged 85–89, and 60 (6.5%) aged ≥ 90 years. 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 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 genitourinary cancers.

Clinical Outcomes

KEY POINTS

• In patients with NSCLC, melanoma, and genitourinary 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 3–4 in 12.2%; adverse events led to treatment discontinuation in 16.1% of patients.

Among response-evaluable patients, objective response rates were 32.2% (complete response in 3.6%) in 276 patients with NSCLC, 39.3% (complete response in 18.2%) in 280 patients with melanoma, and 26.2% (complete response in 4.0%) in 126 patients with genitourinary cancers.

Among all patients, 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) in patients with NSCLC, 11.1 months (95% CI = 8.9–16.0 months) and 30.0 months (95% CI = 23.6–46.4 months) in patients with melanoma, and 6.0 months (95% CI = 5.0–10.7 months) and 15.0 months (95% CI = 9.1–25.4 months) in patients with genitourinary cancers.

In analysis adjusting for sex, stage, prior therapy, and Eastern Cooperative Group performance status, increasing age was not significantly associated with progression-free or overall survival in the NSCLC, melanoma, or genitourinary 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%). 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 the start of 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 3–4), 85–89 years (37.2%, 10.3% grade 3–4), and ≥ 90 years (38.3%, 11.7% grade 3–4).

Discontinuation of immune checkpoint inhibitor treatment due to immune-related adverse events occurred in 137 patients (16.1%), with discontinuation in 64 (46.7%) due to grade 3 or 4 events. Although the incidence of any grade and grade 3 to 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 patient (P = .008).

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 inhibitors].”

The study was supported by the National Cancer Institute, National Institute on Aging, and others.

Abdul Rafeh Naqash, MD, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, and Douglas B. Johnson, MD, Vanderbilt University Medical Center, are the corresponding authors for the JAMA Oncology

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