Indirect Comparison of the Efficacy of Pembrolizumab Versus Nivolumab as Adjuvant Options for Stage IIB/IIC Melanoma

BACKGROUND: Adjuvant anti-PD-1 therapy improves outcomes in resected stage IIB/IIC melanoma at high risk of recurrence; however, no randomized head-to-head trial has directly compared pembrolizumab with nivolumab. OBJECTIVE: The objective was to compare the efficacy of pembrolizumab and nivolumab as adjuvant therapies in resected stage IIB/IIC melanoma using an indirect treatment comparison (ITC). PATIENTS AND METHODS: An anchored Bucher ITC was performed linking the results of KEYNOTE-716 and the CheckMate-76K trials. Primary analyses used the most recent follow-up hazard ratios (HRs), with secondary analyses based on the original trial publications. RESULTS: The ITC showed no statistically significant differences between pembrolizumab and nivolumab for recurrence-free survival (RFS; HR 0.97, 95% confidence intervals (CI) 0.69-1.35) or distant metastasis-free survival (DMFS; HR 0.81, 95% CI 0.54-1.21). Subgroup analyses for RFS were also nonsignificant: stage IIB HR 0.97, 95% CI 0.62-1.50; stage IIC HR 1.00, 95% CI 0.61-1.65; age < 65 years HR 1.20, 95% CI 0.76-1.89; and age ≥ 65 years HR 0.77, 95% CI 0.47-1.25. Secondary analyses based on the original trial publications yielded nonsignificant estimates that numerically favored nivolumab, with RFS HR 1.48 (95% CI 0.98-2.23) and DMFS HR 1.26 (95% CI 0.74-2.13). CONCLUSIONS: This ITC demonstrated no statistically significant differences between pembrolizumab and nivolumab for RFS or DMFS in resected stage IIB/IIC melanoma, with consistently null findings across subgroup analyses. Longer follow-up attenuated earlier numerical trends, with effect estimates converging toward unity.