e21513 Background: Therapies targeting programmed cell death protein 1 (PD1) are mainstays of modern cancer therapy. Pembrolizumab and nivolumab outcomes have not been established in a prospective randomized trial. Comparative analyses in indications where both are used identically may support interchangeability. Retrospective analyses suggest similar outcomes but have not been evaluated in a national US health system. We therefore compared effectiveness and safety outcomes for pembrolizumab versus nivolumab in advanced/unresectable or metastatic melanoma using data from the national Veterans Affairs (VA) health system. Methods: We extracted all pembrolizumab and nivolumab administrations for advanced/unresectable or metastatic melanoma using ICD-9/10 codes and natural language processing (NLP) from January 1, 2015 to July 1, 2025 from the VA’s Corporate Data Warehouse. Patients with known BRAF mutations at immunotherapy initiation and those treated with ipilimumab/nivolumab were excluded. Baseline covariates influencing anti-PD1 prescribing were balanced using propensity score adjustment, with missing data addressed via multiple imputation. 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 irAEs). Propensity-weighted Cox models and Kaplan-Meier estimates were pooled using Rubin’s rules. The VA Ann Arbor Institutional Review Board approved the study. Results: Among 742 patients, 413 (55.7%) received pembrolizumab and 329 (44.3%) nivolumab. Pembrolizumab recipients were older and more likely to have initiated therapy in recent years. Median follow-up was 68 months and 66 months, respectively, with excellent covariate balance after adjustment (standardized difference <0.05). Median TTNT was 14.6 months for pembrolizumab and 13.2 months for nivolumab (adjusted hazard ratio aHR 0.93, 95% CI 0.78, 1.11; p=0.43). Median OS was 27.9 months for pembrolizumab and 25.3 months for nivolumab (aHR 0.97, 95% CI 0.80, 1.17; p=0.73). Two-year cumulative event rates of prolonged corticosteroid use were 22.1% and 23.5%, respectively (aHR 1.02, 95% CI 0.71, 1.47; p=0.93). Conclusions: In this national cohort, pembrolizumab and nivolumab demonstrated equivalent effectiveness as first-line therapies for advanced/unresectable or metastatic melanoma, consistent with an anti-PD1 class effect. Limitations include reliance on ICD coding, lack of randomization, and corticosteroid use as a proxy for irAEs. Given real-world data from different health systems in multiple countries demonstrating near-equivalent outcomes, these findings support pembrolizumab and nivolumab interchangeability.
Nieto et al. (Thu,) studied this question.