Datasets exploring the prognostic value of BRAF mutations in early stage and metastatic melanoma have shown poorer or, at best, equivalent outcomes for BRAF mutant versus wild-type populations. Most cohorts, however, predate the routine use of targeted therapies and thus there is little data looking at the outcomes of patients with BRAF mutant stage IV melanoma in the era of BRAF directed therapies.
We analysed the BRAF mutational status and overall survival of stage IV malignant melanoma patients across three major Australian metropolitan hospitals diagnosed between June 2011 and April 2015. Patients with no recorded mutation status and no documented follow up were excluded. Basic demographics (age, M stage, presence of brain and liver metastases) and treatment received were correlated with mutation status and a multivariate analysis was performed for overall survival.
234 patients were identified, 13 had no recorded mutation status and a further 11 were excluded as they had no treatment or follow up recorded, leaving 210 for analysis. BRAF mutations were present in 43% (90) of patients. 77% (69) of these BRAF positive patients received BRAF +/- MEK inhibitors, the majority as a first line agent (94%). 69% of patient's analysed were stage M1c at stage IV diagnosis, 36% developed brain metastases in the course of their disease and 33% liver metastases. BRAF mutation status was not associated with a survival benefit in univariate (p = 0.195) or multivariate (p = 0.297) analysis. In multivariate analysis liver metastasis (p < 0.001), age (p = 0.010) and M stage (p = 0.001) were the only factors that independently predicted survival.
In our cohort of stage IV melanoma patients, the presence or absence of a BRAF mutation had no significant effect on overall survival. This suggests BRAF mutation status is not a reliable prognostic indicator in the era of targeted therapies.
Clinical trial identification
All authors have declared no conflicts of interest.