Immune Checkpoint Inhibitors May Be Effective, Safe in Geriatric Cancer

Retrospective data suggest survival outcomes were positive and safety was reasonable for patients with cancer aged 80 years or older who received immune checkpoint inhibitors.

Although discontinuations due to adverse effects (AEs) were more frequent with increasing age, treatment with immune checkpoint inhibitors (ICIs) for geriatric patients with cancer appeared to be an effective and well tolerated option, according to the results of an international cohort study published in JAMA Oncology.

After being treated with an ICI, the overall response rates (ORR) were 32.2%, including a 3.6% complete response (CR) rate and 28.6% partial response (PR) rate for patients with non­–small cell lung cancer (NSCLC); 39.3%, including a 18.2% CR rate and 21.1% PR rate for patients with melanoma; and 26.2%, including a 4.0% CR rate and 22.2% PR rate for patients with genitourinary (GU) cancers.

“The findings of this international cohort study suggest that single-agent checkpoint inhibitors may be effective and generally well tolerated in patients older than 80 years, suggesting that age alone should not preclude patients from treatment with ICIs,” the investigators wrote.

Retrospective data were collected from patients with cancer treated between 2010 and 2019 across 18 medical centers in the United States and Europe. The population included patients who were treated with ICIs until the age of 80 years (n = 19) or older than 80 years (n = 909) at ICI initiation.

Clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) were analyzed, as well as immune-related AE (irAE) patterns.

A total of 928 patients were included in the main cohort and treated with anti–PD-1 (n = 806), anti–PD-L1 (n = 79), and anti–CTLA-4 (n = 43) therapies. The median age for the cohort at ICI initiation was 83.0 years (range, 75.8-97.0). Specifically, 67.5% of patients were younger than 85 years, 26.1% were between the ages of 85 and 89 years, and 6.5% were aged 90 years or older. The most common tumor types represented in the research were NSCLC (37.2%), melanoma (35.5%), and GU cancers (16.5%).

ORR for patients with NSCLC younger than 85 years was 34.5% compared with 25.7% for patients 75 years or older (P = .18). For melanoma, the ORRs were 35.8% and 45.5% for patients younger than 85 years and aged 85 years or older, respectively (P = .11). For GU cancers, patients had ORRs of 29.8% vs 19.0% in the 2 groups, respectively (P = .20).

Both PFS and OS were also analyzed across the 3 tumor types. Patients with NSCLC had a median PFS of 6.7 months (95% CI, 5.2-8.6 months) and a median OS of 10.9 months (95% CI, 8.6-13.1 months). The median PFS for patients under the age of 85 years and 85 years or older was 8.0 months (95% CI, 5.6-9.5) and 5.0 months (95% CI, 4.0-8.4), respectively (P = .40). The median OS for these 2 groups was 11.8 months (95% CI, 9.3-15.3) and 7.5 months (95% CI, 5.0-11.5), respectively (P = .047).

For patients with melanoma, the overall median PFS was 11.1 months (95% CI, 8.9-16.0), with a median OS of 30.0 months (95% CI, 23.6-46.4). Among patients younger than 85 years and those 85 years or older, the median PFS was 13.6 months (95% CI, 9.6-22.8) and 7.4 months (95% CI, 5.0-15.0), respectively (P = .23). Median OS for the same groups was 34.2 months (95% CI, 27.8- 47.6) and 24.5 months (95% CI, 13.8-NA), respectively (P = .30).

The median PFS and OS for patients with GU cancers were 6.0 months (95% CI, 5.0-10.7) and 15.0 months (95% CI 9.1-25.4), respectively. For patients younger than 85 years, the median PFS was 6.5 months (95% CI, 5.0-16.6) compared with 6.0 months (95% CI, 3.6-11.2) for patients aged 85 years or older (P = .25). For both groups, the median OS was 15.7 months (95% CI, 11.4-34.9) and 7.2 months (95% CI, 6.6-NA), respectively (P = .13).

At least 1 irAE was observed in 41.3% of patients from the overall patient population, including grade 3/4 irAEs in 12.2% of patients. Common irAEs of any grade included dermatitis (14.2%), colitis/diarrhea (9.2%), and thyroid toxic effects (8.1%). Similar rates of irAEs of any grade were observed across age groups. Discontinuations due to irAEs were reported in 16.1% of patients who received ICIs, 46.7% of which were grade 3/4.

“Randomized clinical trials using ICIs for geriatric patients are needed to further elucidate the clinical effect of our findings and identify histology-specific outcomes using appropriate controls,” the investigators concluded.

Reference

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. Published online November 4, 2021. doi:10.1001/jamaoncol.2021.4960