Pembrolizumab and Nivolumab Show Similar Outcomes in Advanced Melanoma in VA Cohort Study

Pembrolizumab and nivolumab were associated with similar effectiveness and safety as first-line therapy for advanced, unresectable, or metastatic melanoma among US veterans, according to a research letter published in JAMA Network Open.

Both agents are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and are the most used members of the class. However, the investigators noted that their comparative effectiveness and safety have not been established in a prospective randomized clinical trial.

For this propensity score–adjusted comparative effectiveness study, researchers analyzed national Veterans Affairs (VA) health system data from January 1, 2015, to July 1, 2025. Patients with known BRAF variations at immunotherapy initiation were excluded. The cohort included 742 patients, of whom 413 received pembrolizumab and 329 received nivolumab; the median age was 73 years, and 97.4% were male. Median follow-up was 5.6 years for pembrolizumab and 5.5 years for nivolumab.

Median time to next treatment, the primary outcome, was 14.6 months with pembrolizumab and 13.2 months with nivolumab (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.78-1.10), with the confidence interval including the possibility of no difference. Median overall survival was 27.9 months and 25.3 months, respectively (aHR, 0.96; 95% CI, 0.79-1.16). Two-year rates of prolonged, high-dose corticosteroid use, a proxy for clinically significant immune-related adverse events, were 22.1% and 23.5% (aHR, 1.00; 95% CI, 0.70-1.44).

The authors said the findings are consistent with an anti–PD-1 class effect and that the choice between the agents should be a joint decision among patients, payers, and health systems, guided by financial, operational, and logistical factors. They cited limitations including reliance on corticosteroid use as a proxy for immune-related adverse events, potential unmeasured confounding, and a sample size that cannot rule out modest differences in safety or effectiveness, particularly in genomically defined subsets.

Source: Strohbehn GW, Nieto JD, Goldstein DA, Bryant AK. Pembrolizumab vs nivolumab as initial treatment for advanced, unresectable, or metastatic melanoma. JAMA Netw Open. 2026;9(9):e2636432. doi:10.1001/jamanetworkopen.2026.36432