In a meta-analysis reported in JAMA Network Open, Farooq et al found that immune checkpoint inhibitor therapy for cancer was associated with a lower risk of neurologic adverse events compared with treatment with other agents overall in randomized trials comparing immune checkpoint inhibitors with other therapies. Immune checkpoint inhibitors were associated with a lower risk vs chemotherapy and a higher risk vs placebo.
The meta-analysis included phase II or III randomized clinical trials of U.S. Food and Drug Administration–approved immune checkpoint inhibitors reported through March 2020. The risk of neurologic adverse events of any grade were compared between patients who received immune checkpoint inhibitors and a control group consisting of patients in the comparator groups of the trials who received other treatment, including chemotherapy, targeted therapy, vaccines, combination therapies, or placebo. Separate analyses were performed for 15 trials comparing immune checkpoint inhibitors vs chemotherapy and 5 trials comparing immune checkpoint inhibitors vs placebo.
Key Findings
A total of 39 trials were included, with 10,595 patients in the immune checkpoint inhibitor group and 13,110 patients in the control group. Among all patients, 68.0% were male and 33.1% were White. Non–small cell lung cancer was the most common cancer in both groups (39.5% in the immune checkpoint inhibitor group, 37.6% in the control group).
Overall, neurologic adverse events of any grade occurred in 15.0% of the immune checkpoint inhibitor group vs 19.9% of the control group (risk ratio [RR] = 0.59, 95% confidence interval [CI] = 0.45–0.77). Peripheral neuropathy (RR = 0.30, 95% CI = 0.17–0.51) and dysgeusia (RR = 0.41, 95% CI = 0.27–0.63) were significantly less common in the immune checkpoint inhibitor group and headache was significantly more common (RR = 1.32, 95% CI = 1.10–1.59).
Among patients in the 15 trials comparing immune checkpoint inhibitors with chemotherapy, rates of neurologic adverse events were 6.0% vs 17.4% (RR = 0.22, 95% CI = 0.13–0.39). Peripheral neuropathy (RR = 0.09, 95% CI = 0.05–0.17), dysgeusia (RR = 0.42, 95% CI = 0.21–0.85), and paresthesia (RR = 0.29, 95% CI = 0.13–0.67) were significantly less common in the immune checkpoint inhibitor group.
Among patients in the five trials comparing immune checkpoint inhibitors with placebo, rates of neurologic adverse events were 17.5% vs 12.4% (RR = 1.57, 95% CI = 1.30–1.89). Headache was significantly more common in the immune checkpoint inhibitor group (RR = 1.63, 95% CI = 1.32–2.02).
The investigators concluded: “Results of this meta-analysis suggest that the overall risk of [neurologic adverse events], peripheral neuropathy, and dysgeusia is lower with the use of [immune checkpoint inhibitors]. When compared with chemotherapy, the overall risk of [neurologic adverse events], peripheral neuropathy, paresthesia, and dysgeusia was lower with [immune checkpoint inhibitor] use; however, when compared with placebo, the risk of [neurologic adverse events] is higher with the use of [immune checkpoint inhibitors].”
Ankit Mangla, MD, of the Division of Hematology and Oncology, Case Western Reserve University School of Medicine, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
