Effective treatments for patients with cholangiocarcinoma after progression on gemcitabine-based chemotherapy are urgently needed. Mutations in the BRAF gene have been found in 5% of biliary tract tumours. The combination of dabrafenib and trametinib has shown activity in several BRAF^V600E-mutated cancers. We aimed to assess the activity and safety of dabrafenib and trametinib combination therapy in patients with BRAF^V600E-mutated biliary tract cancer.

This study is part of an ongoing, phase 2, open-label, single-arm, multicentre, Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAF^V600E-mutated rare cancers. Patients were eligible for the biliary tract cancer cohort if they were aged 18 years or older, had BRAF^V600E-mutated, unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, an Eastern Cooperative Oncology Group performance status of 0–2, and had received previous systemic treatment. All patients were treated with oral dabrafenib 150 mg twice daily and oral trametinib 2 mg once daily until disease progression or intolerance of treatment. The primary endpoint was the overall response rate, which was determined by Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat evaluable population, which comprised all enrolled patients regardless of receiving treatment who were evaluable (ie, had progression, began a new anticancer treatment, withdrew consent, died, had stable disease for 6 weeks or longer, or had two or more post-baseline assessments). The ROAR trial is registered with ClinicalTrials.gov, NCT02034110. These results are based on an interim analysis; the study is active but not recruiting.

Between March 12, 2014, and July 18, 2018, 43 patients with BRAF^V600E-mutated biliary tract cancer were enrolled to the study and were evaluable. Median follow-up was 10 months (IQR 6–15). An investigator-assessed overall response was achieved by 22 (51%, 95% CI 36–67) of 43 patients. An independent reviewer-assessed overall response was achieved by 20 (47%, 95% CI 31–62) of 43 patients. The most common grade 3 or worse adverse event was increased γ-glutamyltransferase in five (12%) patients. 17 (40%) patients had serious adverse events and nine (21%) had treatment-related serious adverse events, the most frequent of which was pyrexia (eight [19%]). No treatment-related deaths were reported.

Dabrafenib plus trametinib combination treatment showed promising activity in patients with BRAF^V600E-mutated biliary tract cancer, with a manageable safety profile. Routine testing for BRAF^V600E mutations should be considered in patients with biliary tract cancer.

GlaxoSmithKline and Novartis.