BRAF and cholangiocarcinoma: BRAF mutations occur in up to 5% of CCA, with BRAF V600E being the most common alteration.222 Vemurafenib was investigated in a phase II basket trial in patients with BRAF V600E mutated tumors, and one partial response was observed in eight patients with CCA.223 Combination of MEK- (trametinib) and BRAF-inhibition (dabrafenib) was effective in a phase II basket trial (ROAR) in 43 CCA patients with a reported objective response of 51% and a median overall survival of 14 months224, leading to its approval in 2022.