Retrospective study of pembrolizumab versus nivolumab as initial treatment for advanced, unresectable, or metastatic melanoma

A retrospective study using data from the US Veterans Affairs (VA) health system compared effectiveness and safety outcomes of pembrolizumab versus nivolumab as initial treatment for advanced, unresectable, or metastatic melanoma from January 2015 through June 2025. Baseline covariates for patient, temporal, and cancer characteristics thought to influence anti-PD-1 prescribing were balanced using propensity score adjustment.The primary outcome was time-to-next treatment (TTNT); secondary outcomes were overall survival (OS) and prolonged, high-dose corticosteroids (a proxy for clinically significant immune-related adverse events. The cohort included 742 patients who received anti-PD-1 therapy with either pembrolizumab (55.7%) or nivolumab (44.3%); the median age was 73 years (IQR 68-80), and 97.4% were male. Pembrolizumab recipients were older and were more likely to have intiated therapy in recent year. Median follow-up was 5.6 years for the pembrolizumab group and 5.5 years for the nivolumab group. There were no statistacally significant differences between the two groups for TTNT (p=0.38), OS (p=0.66), and two-year cumulative event rates of prolonged, high-dose corticosteroid use (p=0.99). The authors conclude that in this US national cohort with more than 5 years of follow-up, pembrolizumab and nivolumab showed similar effectiveness and safety as first-line therapies for advanced, unresectable, or metastatic melanoma.