Research in context
Evidence before this study
We searched PubMed for clinical studies published up to March 7, 2017, with the search terms “BRAF”, “melanoma”, and “brain metastases”, and identified 144 articles, of which four were primary analyses of phase 1 or 2 clinical trials of BRAF inhibitor regimens in patients with BRAFV600-mutant melanoma brain metastases. BRAF inhibitor monotherapy has previously been shown to have clinical activity and tolerability in patients with BRAF-mutant melanoma who developed metastases in the brain. Although the BRAF and MEK inhibitor combination therapy has been shown to be superior to BRAF inhibitor monotherapy in patients with BRAFV600-mutant metastatic melanoma without brain metastases, the clinical effect of this regimen on melanoma brain metastases has not been characterised.
Added value of this study
Intracranial outcomes showed that dabrafenib plus trametinib was active in patients with BRAFV600-mutant melanoma brain metastases and the primary study endpoint was met; however, responses did not last as long as those previously observed for the combination in patients with melanoma without brain metastases. No unexpected safety issues were observed with dabrafenib plus trametinib in this setting. Our findings represent the first report, to our knowledge, of a phase 2 trial evaluating BRAF and MEK inhibitor combination therapy in patients with melanoma brain metastases and provide evidence that clinical benefit and tolerability are achievable with dabrafenib plus trametinib in a subset of patients with BRAFV600-mutant melanoma that has metastasised to the brain.
Implications of all the available evidence
Continued follow-up in this study is necessary to determine the full effect of dabrafenib plus trametinib on overall survival in this setting; however, these preliminary results support the use of this targeted therapy combination as a treatment option for these patients, in whom effective treatments remain a critical unmet medical need.