Brazilian Journal of Oncology (Oct 2022)

The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis

  • Mauricio Fernando Silva Almeida Ribeiro,
  • Camila Bragança Xavier,
  • Allan Andresson Lima Pereira,
  • Mariana Scaranti,
  • Luiza Dib Batista Bugiato Faria,
  • Tatiana Strava Correa,
  • Marina Sahade,
  • David Queiroz Borges Muniz,
  • Olavo Feher,
  • Gustavo dos Santos Fernandes,
  • Artur Katz,
  • Rodrigo Ramella Munhoz

DOI
https://doi.org/10.5935/2526-8732.20220298
Journal volume & issue
Vol. 18, no. 00

Abstract

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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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