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CC BY 4.0 · Brazilian Journal of Oncology 2022; 18: e-20220298
DOI: 10.5935/2526-8732.20220298
Review Article
Clinical Oncology

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

A adição do bloqueio do eixo PD-1/PD-L1 à inibição de BRAF e MEK para pacientes com melanoma avançado com mutações BRAF: uma revisão sistemática e metanálise
Mauricio Fernando Silva Almeida Ribeiro 
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Camila Bragança Xavier
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Allan Andresson Lima Pereira
2   Hospital Sírio-Libanês, Oncology Center - Brasília - DF - Brazil
,
Mariana Scaranti
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Luiza Dib Batista Bugiato Faria
2   Hospital Sírio-Libanês, Oncology Center - Brasília - DF - Brazil
,
Tatiana Strava Correa
2   Hospital Sírio-Libanês, Oncology Center - Brasília - DF - Brazil
,
Marina Sahade
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
David Queiroz Borges Muniz
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Olavo Feher
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Gustavo dos Santos Fernandes
2   Hospital Sírio-Libanês, Oncology Center - Brasília - DF - Brazil
,
Artur Katz
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
,
Rodrigo Ramella Munhoz
1   Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - Brazil
› Author Affiliations Financial support: None to declare.
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ABSTRACT

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.

RESUMO

Objetivos: Inibidores de checkpoints imunológicos (ICI) e terapias-alvo (TT) tornaram-se opções padrão para melanomas metastáticos (MM) BRAF-V600 mutados. Recentemente, ensaios clínicos randomizados (ECR) abordaram a eficácia das abordagens combinadas, com resultados conflitantes. Procuramos avaliar a eficácia/segurança da combinação de ICI e inibidores BRAF/ MEK de primeira linha (terapia triple) versus BRAF/MEKi (terapia dupla).

Métodos: Realizamos uma revisão sistemática e metanálise de ECR comparando terapia tripla versus dupla publicados no MEDLINE e EMBASE de 2016 a setembro/2020. Obtivemos estimativas de efeito agrupado por meio do modelo de efeitos aleatórios assumindo p<0,05 como estatisticamente significativo.

Resultados: Entre 1.784 estudos, 3 ECR foram selecionados. Os triplets demonstraram melhora na sobrevida livre de progressão (SLP) (HR 0,79-CI 0,68- 0,91, p=0,001) e na sobrevida global (SG) (HR 0,81-CI 0,67-0,98, p=0,03), com maiores taxas de eventos adversos (EAs) graus 3/4, pirexia, artralgia e elevação de aminotransferases de qualquer grau. As taxas de descontinuação de EA de todos os medicamentos permaneceram semelhantes.

Conclusão: A terapia tripla melhorou a SLP e a SG com toxicidades manejaveis. Estes são resultados preliminares e dados maduros sao esperados. RESUMO Descritores: Melanoma; Imunoterapia; Receptor de morte celular programada 1; Proteínas proto-oncogênicas B-raf; Sistema de sinalização MAP kinase.

Keywords:

Melanoma - Programmed Cell Death 1 receptor - Proto-oncogene proteins b-raf - MAP kinase signaling system - Immunotherapy

Descritores:

Melanoma - Imunoterapia - Receptor de morte celular programada 1 - Proteínas proto-oncogênicas B-raf - Sistema de sinalização MAP kinase


Publication History

Received: 29 August 2021

Accepted: 15 October 2021

Article published online:
24 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
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. 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. Brazilian Journal of Oncology 2022; 18: e-20220298.
DOI: 10.5935/2526-8732.20220298
 

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