Comparative Efficacy of Combination Immunotherapy And Targeted Therapy in the Treatment of BRAF -mutant Advanced Melanoma: A Matching-Adjusted Indirect Comparison

Abstract

Aim: Comparison of clinical outcomes of nivolumab + ipilimumab versus BRAF + MEK inhibitors (dabrafenib + trametinib or vemurafenib + cobimetinib) in BRAF-mutant advanced melanoma. Methods: Matching-adjusted indirect comparisons were conducted between nivolumab + ipilimumab (CheckMate 067/069 studies) and BRAF + MEK inhibitors (COMBI-d, COMBI-v and coBRIM studies). Overall survival (OS), progression-free survival and objective response rates were assessed. Results: After adjusting, nivolumab + ipilimumab showed improved OS versus dabrafenib + trametinib (hazard ratio [HR] = 0.64; 95% CI: 0.46–0.89) or vemurafenib + cobimetinib (HR = 0.56; 95% CI: 0.36–0.89); OS outcomes were similar at 1 year, with benefits emerging after 12 months; progression-free survival and objective response rates were similar. Grade 3/4 adverse events occurred in 54.1% with nivolumab + ipilimumab, 31.6% with dabrafenib + trametinib and 59.5% with vemurafenib + cobimetinib. Conclusion: Nivolumab + ipilimumab had significantly improv...