L Ny1, M Hernberg2, M Nyakas3, J Koivunen4, L Oddershede5, M Yoon5, X Wang6, P Guyot7, J Geisler8,9. 1. Department of Oncology, Institute of Clinical Science, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. 2. Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. 3. Oslo University Hospital, Oslo, Norway. 4. Department of Oncology and Radiotherapy, Oulu University Hospital, MRC Oulu, Oulu, Finland. 5. Novartis Healthcare A/S, Copenhagen, Denmark. 6. Commercialization & Outcomes, ICON plc, Stockholm, Sweden. 7. Commercialization & Outcomes, ICON plc, Lyon, France. 8. Institute of Clinical Medicine, Campus AHUS, University of Oslo, Oslo, Norway. 9. Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
Abstract
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.
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.
Authors: Konstantinos Christofyllakis; Claudia Pföhler; Moritz Bewarder; Cornelia S L Müller; Lorenz Thurner; Torben Rixecker; Thomas Vogt; Stephan Stilgenbauer; Krista Yordanova; Dominic Kaddu-Mulindwa Journal: Front Oncol Date: 2021-02-18 Impact factor: 6.244
Authors: Charlene M Mantia; Lillian Werner; Brian Stwalley; Corey Ritchings; Ahmad A Tarhini; Michael B Atkins; David F McDermott; Meredith M Regan Journal: Melanoma Res Date: 2022-02-01 Impact factor: 3.599
Authors: Margaret Ottaviano; Emilio Francesco Giunta; Marianna Tortora; Marcello Curvietto; Laura Attademo; Davide Bosso; Cinzia Cardalesi; Mario Rosanova; Pietro De Placido; Erica Pietroluongo; Vittorio Riccio; Brigitta Mucci; Sara Parola; Maria Grazia Vitale; Giovannella Palmieri; Bruno Daniele; Ester Simeone Journal: Int J Mol Sci Date: 2021-03-27 Impact factor: 5.923