Nivolumab Plus Relatlimab Versus BRAF/MEK Inhibitors in BRAF-Mutant Advanced Melanoma

Abstract:

Dual immuno-oncology therapy and BRAF/MEK inhibitor combinations are approved first-line treatment options for BRAF-mutant advanced melanoma. In the absence of head-to-head trials comparing first-line nivolumab plus relatlimab with BRAF/MEK inhibitors, this study compared nivolumab plus relatlimab with dabrafenib plus trametinib, encorafenib plus binimetinib, vemurafenib plus cobimetinib, and atezolizumab plus vemurafenib plus cobimetinib using matching-adjusted indirect comparisons.

Patient-level data for nivolumab plus relatlimab from the RELATIVITY-047 trial BRAF-mutant subset were compared with aggregate data from COMBI-d/v, COLUMBUS, coBRIM, and IMspire150. Adults with untreated BRAF-mutant advanced melanoma receiving first-line therapy were included. Separate unanchored matching-adjusted indirect comparisons were conducted to compare overall survival, progression-free survival, overall response rate, and safety outcomes.

BRAF-mutant patients from RELATIVITY-047 were matched to patients who received dabrafenib plus trametinib, encorafenib plus binimetinib, vemurafenib plus cobimetinib, or atezolizumab plus vemurafenib plus cobimetinib. Post-matching, nivolumab plus relatlimab was associated with longer overall survival after 12 months compared with multiple BRAF/MEK inhibitor regimens and showed more favorable or comparable safety outcomes. Progression-free survival was shorter in the early treatment period compared with some targeted therapy regimens but favored nivolumab plus relatlimab after 12 months in several comparisons. Overall response rate was lower with nivolumab plus relatlimab versus all comparators.

These matching-adjusted indirect comparisons suggest that first-line dual immuno-oncology therapy with nivolumab plus relatlimab may confer a long-term overall survival advantage in BRAF-mutant advanced melanoma compared with BRAF/MEK inhibitor combinations despite lower response rates. As unanchored analyses, potential residual confounding remains, and results should be interpreted cautiously.

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 Oncology. 2025;4:e000912. doi: 10.1136/bmjonc-2025-000912.