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Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma

INTRODUCTION: The present study aimed to inform an economic evaluation of dabrafenib and trametinib combination as first-line treatment of metastatic melanoma in a Canadian setting. A network meta-analysis was conducted to estimate hazard ratios (HRs) for progression-free survival (PFS)and overall s...

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Autores principales: Amdahl, Jordan, Chen, Lei, Delea, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315084/
https://www.ncbi.nlm.nih.gov/pubmed/28261653
http://dx.doi.org/10.1007/s40487-016-0030-2
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author Amdahl, Jordan
Chen, Lei
Delea, Thomas E.
author_facet Amdahl, Jordan
Chen, Lei
Delea, Thomas E.
author_sort Amdahl, Jordan
collection PubMed
description INTRODUCTION: The present study aimed to inform an economic evaluation of dabrafenib and trametinib combination as first-line treatment of metastatic melanoma in a Canadian setting. A network meta-analysis was conducted to estimate hazard ratios (HRs) for progression-free survival (PFS)and overall survival (OS) of dabrafenib plus trametinib versus other first-line treatments of BRAF mutation-positive metastatic melanoma including dabrafenib, trametinib, vemurafenib, ipilimumab, and dacarbazine (DTIC). METHODS: HRs for PFS and OS were from randomized controlled trials identified from systematic literature reviews. HRs for PFS and OS (adjusted for crossover as appropriate) were analyzed using multivariate and univariate Bayesian network meta-analysis. RESULTS: In multivariate network-meta analyses (HRs for PFS and OS estimated simultaneously to account for the correlation of treatment effects on PFS and OS), HRs (95% credible interval) for PFS and OS favored dabrafenib plus trametinib [PFS: 0.23 (0.18–0.29) versus DTIC, 0.32 (0.24–0.42) versus ipilimumab plus DTIC, 0.52 (0.32–0.83) versus trametinib, 0.57 (0.48–0.69) versus vemurafenib, and 0.59 (0.50–0.71) versus dabrafenib]; OS [0.41 (0.29–0.56) versus DTIC, 0.52 (0.38–0.71) versus ipilimumab plus DTIC, 0.68 (0.47–0.95) versus trametinib, 0.69 (0.57–0.84) versus vemurafenib, and 0.72 (0.60–0.85) versus dabrafenib]. The beneficial effects on OS of dabrafenib plus trametinib versus ipilimumab plus DTIC and versus trametinib were attenuated when HRs were estimated using univariate network meta-analysis (HRs for PFS and OS estimated separately). CONCLUSION: This analysis demonstrates improved PFS and OS with dabrafenib + trametinib versus dabrafenib, trametinib, vemurafenib, ipilimumab plus DTIC, and DTIC as first-line treatment for patients with BRAF mutation-positive metastatic melanoma. FUNDING: Novartis Pharmaceuticals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40487-016-0030-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-53150842017-03-02 Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma Amdahl, Jordan Chen, Lei Delea, Thomas E. Oncol Ther Original Research INTRODUCTION: The present study aimed to inform an economic evaluation of dabrafenib and trametinib combination as first-line treatment of metastatic melanoma in a Canadian setting. A network meta-analysis was conducted to estimate hazard ratios (HRs) for progression-free survival (PFS)and overall survival (OS) of dabrafenib plus trametinib versus other first-line treatments of BRAF mutation-positive metastatic melanoma including dabrafenib, trametinib, vemurafenib, ipilimumab, and dacarbazine (DTIC). METHODS: HRs for PFS and OS were from randomized controlled trials identified from systematic literature reviews. HRs for PFS and OS (adjusted for crossover as appropriate) were analyzed using multivariate and univariate Bayesian network meta-analysis. RESULTS: In multivariate network-meta analyses (HRs for PFS and OS estimated simultaneously to account for the correlation of treatment effects on PFS and OS), HRs (95% credible interval) for PFS and OS favored dabrafenib plus trametinib [PFS: 0.23 (0.18–0.29) versus DTIC, 0.32 (0.24–0.42) versus ipilimumab plus DTIC, 0.52 (0.32–0.83) versus trametinib, 0.57 (0.48–0.69) versus vemurafenib, and 0.59 (0.50–0.71) versus dabrafenib]; OS [0.41 (0.29–0.56) versus DTIC, 0.52 (0.38–0.71) versus ipilimumab plus DTIC, 0.68 (0.47–0.95) versus trametinib, 0.69 (0.57–0.84) versus vemurafenib, and 0.72 (0.60–0.85) versus dabrafenib]. The beneficial effects on OS of dabrafenib plus trametinib versus ipilimumab plus DTIC and versus trametinib were attenuated when HRs were estimated using univariate network meta-analysis (HRs for PFS and OS estimated separately). CONCLUSION: This analysis demonstrates improved PFS and OS with dabrafenib + trametinib versus dabrafenib, trametinib, vemurafenib, ipilimumab plus DTIC, and DTIC as first-line treatment for patients with BRAF mutation-positive metastatic melanoma. FUNDING: Novartis Pharmaceuticals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40487-016-0030-2) contains supplementary material, which is available to authorized users. Springer Healthcare 2016-09-27 /pmc/articles/PMC5315084/ /pubmed/28261653 http://dx.doi.org/10.1007/s40487-016-0030-2 Text en © The Author(s) 2016 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Amdahl, Jordan
Chen, Lei
Delea, Thomas E.
Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title_full Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title_fullStr Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title_full_unstemmed Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title_short Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma
title_sort network meta-analysis of progression-free survival and overall survival in first-line treatment of braf mutation-positive metastatic melanoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315084/
https://www.ncbi.nlm.nih.gov/pubmed/28261653
http://dx.doi.org/10.1007/s40487-016-0030-2
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