Dabrafenib-trametinib combination effective in BRAF-mutated cholangiocarcinoma

August 2020 Cancer trials Jolien Blokken
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To date, patients with cholangiocarcinoma who progress on gemcitabine-based chemotherapy have limited treatment options at their disposal and novel, effective treatment regimens are urgently needed. As approximately 5% of patients with biliary tract tumours have mutations in their BRAF gene, the combination of the BRAF-inhibitor dabrafenib with the MEK-inhibitor trametinib can represent a promising treatment combination for these patients.

The ROAR study is an ongoing, phase II, open-label, single-arm, multicentre basket trial in patients with BRAFV600E-mutated rare cancers. In total, 43 patients with BRAFV600E-mutated biliary tract cancer were enrolled to the biliary tract cancer cohort of the study, all of which had received previous systemic treatment. All patients received oral dabrafenib 150 mg, twice daily in combination with oral trametinib 2 mg, once daily until disease progression or intolerance to the treatment regimen.

Targeted therapy achieves a 51% overall response rate

After a median follow-up of 10 months, an investigator-assessed overall response was achieved in 22 out of the 43 patients (51%, 95%CI: 36-67). An independent reviewer-assessed overall response was achieved by 20 (47%, 95%CI: 31-62) of 43 patients. The median duration of response was 8.7 months, with seven patients seeing an ongoing response beyond 12 months. The median progression-free survival was reported at 9.1 months. The median overall survival was 13.5 months, with 56.4% and 35.8% of patients still alive at 12 months and 24 months, respectively. The most common adverse events were fever, nausea, vomiting, diarrhoea and fatigue. The most commonly experienced grade 3 or worse adverse event (12% of patients) was an increased gamma-glutamyltransferase level. Overall, 40% of the patients had a serious adverse event and 21% had treatment-related serious adverse events, of which pyrexia was the most common (19%). No treatment-related deaths were reported.

In conclusion, the dabrafenib-trametinib combination demonstrated promising activity in patients with BRAFV600E-mutated biliary tract cancer and has a manageable safety profile. Routine testing for BRAFV600Emutations in patients with cholangiocarcinoma should therefore be considered.


Subbiah V, Lassen U, Elez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020 [online ahead of print]. DOI:https://doi.org/10.1016/S1470-2045(20)30321-1.