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. 2020 Mar;33(2):e13145.
doi: 10.1111/dth.13145. Epub 2019 Nov 14.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis

Nathaly Garzón-Orjuela  1 , Laura Prieto-Pinto  1 , Pieralessandro Lasalvia  1 , Daniel Herrera  2 , Johanna Castrillón  3 , Diana González-Bravo  1 , Camilo Castañeda-Cardona  1 , Diego Rosselli  1   4
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Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis

Nathaly Garzón-Orjuela et al. Dermatol Ther. 2020 Mar.

Abstract

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.

Keywords: antineoplastics agents; melanoma; network meta-analysis; progression-free survival; survival.

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References

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