Michael A. Davies, MD
A phase II trial has shown that the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinst) produces responses in brain metastases in patients with BRAF V600–mutant melanoma. These findings were reported by Michael A. Davies, MD, of The University of Texas MD Anderson Cancer Center, and colleagues in The Lancet Oncology.
In this ongoing study, 125 patients with melanoma brain metastases from 32 sites in Europe, North America, and Australia were enrolled between February 2014 and August 2016 in cohorts according to the presence of BRAF V600E–positive asymptomatic metastases with no previous local brain therapy (cohort A, n = 76) or with previous local therapy (cohort B, n = 16) or BRAF V600D/K/R–positive asymptomatic (cohort C, n = 16) or symptomatic (cohort D, n = 17) metastases with or without previous local brain therapy. All patients received dabrafenib at 150 mg twice per day plus trametinib at 2 mg once per day. The primary endpoint was intracranial response in cohort A.
At data cutoff, median follow-up was 8.5 months. Intracranial response occurred in 58% of cohort A patients, 56% of cohort B, 44% of cohort C, and 59% of cohort D. The median durations of response were 6.5, 7.3, 8.3, and 4.5 months in the 4 cohorts.
Among all patients, grade 3 or 4 adverse events occurred in 48%, and serious adverse events occurred in 35%. The most common treatment-related serious adverse events were pyrexia for dabrafenib (6%) and decreased ejection fraction for trametinib (4%).
The investigators concluded: “Dabrafenib plus trametinib was active with a manageable safety profile in this melanoma population that was consistent with previous dabrafenib plus trametinib studies in patients with BRAF V600-mutant melanoma without brain metastases, but the median duration of response was relatively short. These results provide evidence of clinical benefit with dabrafenib plus trametinib and support the need for additional research….”
Davies MA, et al: Lancet Oncol 18:863-873, 2017. ■