Patients with biliary tract cancer often experience disease relapse after gemcitabine-based chemotherapy, representing an area of need in this patient population. In 5% of biliary tract tumors, a mutation in the BRAF gene is found. Dabrafenib in combination with trametinib has been shown to be an effective treatment option for patients with BRAFV600E – mutated cancers, particularly those with biliary tract cancer, according to a recent study, results of which were published in The Lancet Oncology.
Rare Oncology Agnostic Research (ROAR) (NCT02034110), an open-label, single-arm, multicenter, phase 2 trial, enrolled 43 patients with BRAFV600E – mutated biliary tract cancer. To be eligible for the registration, participants had to be 18 years or older, have BRAFV600E -mutated, unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had to have received prior systemic treatment. Patients were administered 150 mg of dabrafenib to be taken orally twice daily and 2 mg of trametinib to be taken orally once daily. Treatment continued until disease progression or intolerance. Primary end point was overall response rate (ORR), as determined by Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat evaluable population.
After a median follow-up of 10 months, the researchers found the ORR to be 51%. The most common treatment-related adverse event of grade 3 or worse was found to be increased γ-glutamyltransferase, which occurred in 12% of patients. Pyrexia, occurring in 19%, was another common side effect.
Study authors, led by Vivek Subbiah, MD, of the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, conclude with important advice for community oncologists: "Routine testing for BRAFV600E mutations should be considered in patients with biliary tract cancer."
For More Information
Clinicaltrials.gov (2020). Efficacy and safety of the combination therapy of dabrafenib and trametinib in subjects with BRAF V600E-mutated rare cancers. NLM Identifier: NCT02034110
Subbiah V, Lassen U, Elez E, et al (2020). Dabrafenib plus trametinib in patients with BRAFV600E – mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicenter basket trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(20)30321-1
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