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Ribeiro, Mauricio Fernando Silva Almeida; Xavier, Camila Bragança; Pereira, Allan Andresson Lima; Scaranti, Mariana; Faria, Luiza Dib Batista Bugiato; Correa, Tatiana Strava; Sahade, Marina; Muniz, David Queiroz Borges; Feher, Olavo; Fernandes, Gustavo dos Santos; Katz, Artur; Munhoz, Rodrigo Ramella
Brazilian Journal of Oncology, 10/2022, Volume: 18Journal Article
Objectives: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF-V600 metastatic melanomas (MM). Recently, randomized trials (RCT) addressed the efficacy of combined approaches, with conflicting results. We sought to evaluate efficacy and safety of first-line combination ICI and BRAF/MEK inhibitors (triplets) versus BRAF/MEKi (doublets). Methods: We performed a systematic review and metaanalysis of RCT comparing triplet versus doublet published in MEDLINE and EMBASE from 2016-September/2020. We obtained pooled effect estimates through random-effects model assuming p<0.05 as statistically significant. Results: Among 1,784 studies, 3 RCT were selected. Triplets demonstrated progression-free survival (PFS) (HR 0.79 - CI 0.68-0.91, p=0.001) and overall survival (OS) improvement (HR 0.81 - CI 0.67-0.98, p=0.03), with increased rates of grades 3/4 adverse events (AEs), any grade pyrexia, arthralgia, and aminotransferases elevation. AEdiscontinuation rates of all drugs remained similar. Conclusions: Triplets improved PFS and OS with manageable toxicities. These are preliminary results and mature data are expected.
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