University of Oulu

L. Ny, M. Hernberg, M. Nyakas, J. Koivunen, L. Oddershede, M. Yoon, X. Wang, P. Guyot & J. Geisler (2020) BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis, Acta Oncologica, 59:7, 833-844, DOI: 10.1080/0284186X.2020.1747636

BRAF mutational status as a prognostic marker for survival in malignant melanoma : a systematic review and meta-analysis

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Author: Ny, L.1; Hernberg, M.2; Nyakas, M.3;
Organizations: 1Department of Oncology, Institute of Clinical Science, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
2Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
3Oslo University Hospital, Oslo, Norway
4Department of Oncology and Radiotherapy, Oulu University Hospital, MRC Oulu, Oulu, Finland
5Novartis Healthcare A/S, Copenhagen, Denmark
6Commercialization & Outcomes, ICON plc, Stockholm, Sweden
7Commercialization & Outcomes, ICON plc, Lyon, France
8Institute of Clinical Medicine, Campus AHUS, University of Oslo, Oslo, Norway
9Department of Oncology, Akershus University Hospital, Lørenskog, Norway
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
Persistent link:
Language: English
Published: Informa, 2020
Publish Date: 2020-12-02


Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).

Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies.

Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09–1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I–III melanoma (combined HR: 1.16, 95% CI: 0.92–1.46), and on PFS in stage III–IV (HR: 0.98 (95% CI: 0.68−1.40)).

Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.

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Series: Acta oncologica
ISSN: 0284-186X
ISSN-E: 1651-226X
ISSN-L: 0284-186X
Volume: 59
Issue: 7
Pages: 833 - 844
DOI: 10.1080/0284186X.2020.1747636
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3122 Cancers
Copyright information: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.