Dabrafenib plus Trametinib for BRAF V600E-Mutated Biliary Tract Cancer

Treatment options for metastatic cholangiocarcinoma beyond initial gemcitabine-based therapy are limited. Next-generation sequencing has identified potential targetable mutations as well as molecular heterogeneity, based on the primary tumor location in the gallbladder, intrahepatic, or extrahepatic bile ducts. Recent regulatory approval was obtained for the FGFR2 inhibitor pemigatinib in patients with cholangiocarcinoma harboring an FGFR2 gene fusion.

Investigators now report results of an industry-sponsored, international, open-label, single-arm, phase II basket trial (ROAR) of the BRAF inhibitor dabrafenib (150 mg twice daily) plus the MEK inhibitor trametinib (2 mg once daily) in 43 patients with cholangiocarcinoma harboring a BRAF V600E mutation who had progression on prior standard therapy. Most patients (91%) had intrahepatic primaries (91%), most were Caucasian (91%), and most were female (56%).

At a median follow-up of 10 months, independent reviewer-assessed response was seen in 47% of patients, with a median duration of response of 9 months. Median progression-free survival was 9 months, and median overall survival was 14 months. More than half of patients (56%) had adverse events leading to dose interruption, and 21% had serious treatment-related adverse events, most commonly pyrexia (19%).