ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort

ROAR (NCT02034110) was a phase 2, open-label, single-arm, multicentre basket trial of dabrafenib plus trametinib in BRAF V600E-mutated rare cancers across nine cohorts (anaplastic thyroid, biliary tract, gastrointestinal stromal tumour, small-bowel adenocarcinoma, low- and high-grade glioma, hairy cell leukaemia, multiple myeloma and adenocarcinoma of unknown primary). The biliary tract cohort enrolled 43 previously treated patients between 2014 and 2018; investigator-assessed overall response, the primary endpoint, was achieved by 22 of 43 (51 percent, 95 percent confidence interval 36 to 67) and independent-review response by 20 of 43 (47 percent), at a median follow-up of 10 months. The most common grade 3 or worse adverse event was raised gamma-glutamyltransferase (12 percent); 40 percent had serious adverse events, 21 percent treatment-related, most often pyrexia. BRAF V600E is found in about 5 percent of biliary tract tumours and is less common in gallbladder cancer than in intrahepatic cholangiocarcinoma. The FDA approved dabrafenib with trametinib for BRAF V600E solid tumours on a tumour-agnostic basis in June 2022 with ROAR among the supporting trials; NCCN lists the pair for biliary cancer, and in the UK the combination is not appraised by NICE for biliary cancer.