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

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

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 fir...

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Main Authors: 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
Format: Article
Language:English
Published: Sociedade Brasileira de Oncologia Clínica, Sociedade Brasileira de Cirurgia Clínica and Sociedade Brasileira de Radioterapia 2022-10-01
Series:Brazilian Journal of Oncology
Subjects:
melanoma
programmed cell death 1 receptor
proto-oncogene proteins b-raf
map kinase signaling system
immunotherapy
Online Access:https://www.brazilianjournalofoncology.com.br/details/189/en-US/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-m
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Summary: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.
ISSN:2526-8732

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