Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma.

Autor: Consoli F; Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST-Spedali Civili, Brescia, Italy., Bersanelli M; Oncology Unit, University Hospital of Parma, Parma, Italy., Perego G; Università Degli Studi Di Milano, Facoltà Di Farmacia, Pharmacy Unit, ASST Bergamo Ovest, Treviglio, BG, Italy., Grisanti S; Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST-Spedali Civili, Brescia, Italy., Merelli B; Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy., Berruti A; Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST-Spedali Civili, Brescia, Italy., Petrelli F; Oncology Unit, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy. faupe@libero.it.
Jazyk: angličtina
Zdroj: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2020 Jun; Vol. 22 (6), pp. 900-907. Date of Electronic Publication: 2019 Sep 25.
DOI: 10.1007/s12094-019-02207-7
Abstrakt: Backgroud: Synergistic combinations between BRAF and MEK inhibitors, such as dabrafenib plus trametinib, vemurafenib plus cobimetinib or encorafenib plus binimetinib, represent the current standard of care in metastatic or locally advanced BRAF V600 mutated malignant melanomas (MM). However, no studies explored the direct head-to-head comparison between the three different combinations. In this paper, we performed a network meta-analysis to evaluate their efficacy in terms of overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety profile.
Method: We performed a systematic review of the literature about published first line trials of BRAF and MEK inhibitors doublets in advanced mutated malignant melanoma. We compared then the results with an adjusted indirect analysis of randomized-controlled trials. Our primary survival outcome was OS. Secondary endpoints were PFS, ORR, G3-4 toxicities described in at least 5% of patients in experimental arms.
Results: We identified three phase-3 trials: coBRIM (vemurafenib and cobimetinib), COMBI-v (dabrafenib and trametinib) and Columbus study (encorafenib and binimetinib) for a total of 1230 included patients. The control arm was vemurafenib in all studies. The indirect comparison revealed no statistically differences for OS, PFS and ORR across trials, while safety profile differed between the three couples of agents.
Conclusion: This indirect adjusted meta-analysis suggests a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM.
Databáze: MEDLINE
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