Improved outcomes in women with BRAF-mutant melanoma treated with BRAF/MEK-targeted therapy across randomized clinical trials. A systematic review and meta-analysis.

Autor:	Pala L; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy. Electronic address: laura.pala@gavazzeni.it., De Pas T; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Pagan E; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy., Minucci S; Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Catania C; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Digiacomo N; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Cocorocchio E; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Laszlo D; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Di Muzio A; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy., Barigazzi C; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy., Stucchi E; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy., De Grandi L; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy., Stucchi S; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy., Viale G; Department of Pathology, European Institute of Oncology & University of Milan, Milan, Italy., Gelber RD; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Harvard T.H. Chan School of Public Health and Frontier Science & Technology, Research Foundation, Boston, MA, USA., Bagnardi V; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy., Conforti F; Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy.
Jazyk:	angličtina
Zdroj:	Seminars in oncology [Semin Oncol] 2023 Feb-Apr; Vol. 50 (1-2), pp. 34-39. Date of Electronic Publication: 2023 Mar 21.
DOI:	10.1053/j.seminoncol.2023.03.003
Abstrakt:	Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients' gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41-0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54-0.74), P-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48-0.80) in women and only 0.78, (95%CI 0.67-0.92) in men, P-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness. Competing Interests: Conflicts of interest None. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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