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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients

Authors: Adil Daud, Japinder Gill, Sheily Kamra, Lei Chen, Amit Ahuja

Published in: Journal of Hematology & Oncology | Issue 1/2017

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Abstract

Background

Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies.

Methods

A systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]).

Results

The indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 − 1.30), PFS (HR 1.05, 95% CI 0.79 − 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 − 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 − 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 − 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 − 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib.

Conclusions

This indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.
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Metadata
Title
Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients
Authors
Adil Daud
Japinder Gill
Sheily Kamra
Lei Chen
Amit Ahuja
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-016-0369-8

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