Phase II, open-label study of dabrafenib plus trametinib in patients with BRAF mutation-positive melanoma brain metastases: A GSK-sponsored trial.

TPS9106 Background: Data from BREAK-MB (phase II, metastatic melanoma, BRAF V600 mutation positive, with brain metastases, dabrafenib monotherapy) demonstrated a 39.2% overall intracranial response rate and a 81.1% intracranial disease control in cohort A (no prior local therapy), and a 30.8% overall intracranial response rate and a 89.2% intracranial disease control in cohort B (previous local therapy). Median survival was 33.1 and 31.4 weeks for cohorts A and B, respectively. [Long G, et al. Lancet Oncol. 2012;13:1087-95]. Data from BRF113220 (phase I/II, metastatic melanoma, BRAF V600 mutation-positive, brain metastasis patients excluded, dabrafenib + trametinib) reported a median progression-free survival (PFS) of 9.4 months with dabrafenib 150mg BID and trametinib 2mg QD combination therapy (150/2), and 5.8 months with dabrafenib monotherapy (HR 0.39, p<0.0001). [Flaherty K, et al. N Engl J Med. 2012;367(18):1694-703] The median overall survival for the 150/2 therapy was 23.8 months compared with 20....