Citation
Miller DM, Smithy JW, Palaia J, Patel D, Salvatore A, D'Adamo D, Mattera M, Zhou ZY, Garcia-Horton V, Tarhini AA. Efficacy of nivolumab plus relatlimab versus BRAF/MEK inhibitors for first-line treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. BMJ Oncol. 2025;4:e000912. doi:10.1136/bmjonc-2025-000912.
Overview
Dual immune checkpoint blockade and BRAF/MEK inhibitor combinations are both approved first-line options for patients with BRAF-mutant advanced melanoma. In the absence of head-to-head trials comparing nivolumab plus relatlimab with targeted therapy, this study used unanchored matching-adjusted indirect comparisons to estimate relative efficacy and safety.
Patient-level data from the BRAF-mutant subgroup of RELATIVITY-047 were matched to aggregate data from COMBI-d/v, COLUMBUS, coBRIM, and IMspire150. Outcomes included overall survival, progression-free survival, overall response rate, and safety.
Nivolumab plus relatlimab may offer a longer-term overall survival advantage over several BRAF/MEK inhibitor regimens despite lower initial response rates and less favorable early progression-free survival. Because these were unanchored indirect comparisons, residual confounding remains possible and the findings should be interpreted cautiously.
Comparators
Dabrafenib + Trametinib
Compared using aggregate data from COMBI-d and COMBI-v.
Encorafenib + Binimetinib
Compared using aggregate data from COLUMBUS.
Vemurafenib + Cobimetinib
Compared using aggregate data from coBRIM.
Atezolizumab + Vemurafenib + Cobimetinib
Compared using aggregate data from IMspire150.
Key findings
Overall survival
After matching, nivolumab plus relatlimab was associated with longer overall survival beyond 12 months versus multiple targeted therapy regimens.
Progression-free survival
Early progression-free survival favored some targeted regimens, whereas later comparisons favored nivolumab plus relatlimab in several analyses.
Overall response rate
Overall response rate was lower with nivolumab plus relatlimab than with each BRAF/MEK inhibitor comparator.
Safety
Nivolumab plus relatlimab demonstrated favorable or broadly comparable safety outcomes across multiple comparisons.
Interpretive considerations
- No head-to-head randomized trial directly compared nivolumab plus relatlimab with the included BRAF/MEK inhibitor regimens.
- Separate unanchored MAICs were required for each comparator.
- Observed differences may reflect residual confounding from unmeasured or incompletely matched patient characteristics.
- Lower response rates do not necessarily preclude a longer-term survival advantage.
- The findings support consideration of long-term treatment goals when selecting first-line therapy for BRAF-mutant advanced melanoma.
Authors
David M. Miller, James W. Smithy, Jennell Palaia, Divya Patel, Anthony Salvatore, David D'Adamo, Matthew Mattera, Zheng-Yi Zhou, Viviana Garcia-Horton, and Ahmad A. Tarhini.