Matching-Adjusted Indirect Comparison (MAIC) of Nivolumab + Relatlimab (NIVO+RELA) Vs. BRAF/MEK Inhibitors for First-Line Treatment of BRAF-Mutant Advanced/Metastatic Melanoma (AMEL)

OBJECTIVES: Due to lack of head-to-head randomized clinical trials comparing NIVO+RELA vs BRAF/MEK inhibitors for first-line treatment of BRAF-mutant aMel, we evaluated the efficacy of NIVO+RELA vs dabrafenib+trametinib (DAB+TRAM), encorafenib+binimetinib (ENCO+BINI), and vemurafenib+cobimetinib (VEM+COBI) via MAICs.

METHODS: Patient-level data for NIVO+RELA from the RELATIVITY-047 trial (BRAF-mutant cohort) and aggregate data from the COMBI-d/v (DAB+TRAM), COLUMBUS (ENCO+BINI), and coBRIM (VEM+COBI) trials were utilized for this analysis. Based on data availability and clinical input, all three MAICs matched on baseline age, sex, Eastern Cooperative Oncology Group status, lactate dehydrogenase level, and metastatic stage; DAB+TRAM was additionally matched on number of disease sites and prior immunotherapy, ENCO+BINI on prior immunotherapy, and VEM+COBI on history of brain metastases. MAICs for overall survival (OS) and investigator-assessed progression-free survival (PFS–INV) were performed using weighted Cox proportional hazards models and, due to violation of the proportional hazards assumption, interval Cox models with a boundary point at 12 months. Investigator-assessed overall response rate (ORR–INV) was compared via odds ratios (ORs).

RESULTS: The subset of 136 BRAF-mutant patients from RELATIVITY-047 were matched to 563 patients receiving DAB+TRAM from COMBI-d/v; effective sample size (ESS) for NIVO+RELA was 100. Versus DAB+TRAM after matching, NIVO+RELA was associated with improved OS after 12 months from treatment initiation (hazard ratio [HR] 0.49, 95% confidence interval 0.32–0.75), lower ORR-INV (OR 0.38, 0.28–0.52) and numerically improved PFS–INV (HR 0.61, 0.36–1.05), while no differences in results were observed before 12 months. Similar trends were observed versus ENCO+BINI and VEM+COBI, except NIVO+RELA had lower PFS–INV from 0–12 months than ENCO+BINI and longer PFS–INV after 12 months than COBI+VEMU (ENCO+BINI: 192 patients, ESS=77; VEM+COBI: 247 patients, ESS=111).

CONCLUSIONS: These MAICs suggest long-term (after 12 months) OS advantage of NIVO+RELA over DAB+TRAM, ENCO+BINI, and COBI+VEM for first-line treatment of BRAF-mutant aMel.