Biliary tract cancer (cholangiocarcinoma) is a type of cancer that occurs in the bile ducts. Around 5% of biliary tract tumors comprise mutations in the BRAF gene. Combination therapy with dabrafenib and trametinib has shown activity against the BRAF-V600E gene. This study aims to evaluate the activity and safety of dabrafenib-trametinib combination therapy in patients with BRAF-V600E-mutated biliary tract cancer.

This multicenter, single-arm, open-label, phase-2 basket trial included a total of 43 patients aged 18 years or older with BRAF-V600E-mutated biliary tract cancer (unresectable, metastatic, recurrent, or locally advanced). All the patients were assigned to receive oral dabrafenib 150 mg twice daily and oral trametinib 2 mg twice daily. The primary outcome of the study was the overall response rate.

During the median follow-up of 10 months, 22 patients (51%) achieved the overall response (investigator-assessed). In addition, 20 patients (47%) achieved a reviewer-assessed overall response. The only common adverse event (grade 3 or worse) was increased γ-glutamyltransferase (12%). Besides, 17 patients (40%) had serious adverse events, and 9 (21%) had treatment-related severe events, but no treatment-related deaths occurred.

The research concluded that dabrafenib-trametinib combination therapy exhibited positive outcomes in patients with BRAF-V600E-mutated biliary tract cancer with minimal adverse outcomes.