Phase 2 Study Shows Promise for Dabrafenib, Trametinib Combo in BRAFV600E-Mutated Biliary Tract Cancer

Researchers indicated that results of this study suggest the combination of dabrafenib and trametinib could serve as a much-needed treatment option for patients with BRAFV600E-mutated biliary tract cancer.

Results from a phase 2 study published in The Lancet Oncology showed promising activity with the combination treatment of dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with BRAFV600E-mutated biliary tract cancer.1

In addition, the targeted therapy combination also demonstrated a manageable safety profile in this patient population with treatment-resistant advanced disease. Altogether, these study results suggest the combination of dabrafenib and trametinib could serve as a much-needed treatment option for patients with BRAFV600E-mutated biliary tract cancer.

“In this study, we saw that the dabrafenib and trametinib combination demonstrates clinical benefit and should be considered as a therapeutic option for these patients,” lead author Vivek Subbiah, MD, associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, said in a press release.2 “These findings also reinforce the need for routine testing of BRAF mutations in patients with biliary tract cancers. As we move forward with precision oncology, we’re seeing that alterations present in these rare cancers are actionable and the patients do benefit from targeted therapies.”

This study is part of the ongoing phase 2, open-label, single-arm, multicenter Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAFV600E-mutated rare cancers. Patients eligible specifically for the biliary tract cancer cohort were aged 18 years or older, had BRAFV600E-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.

In total, 43 patients considered evaluable were treated with 150 mg of oral dabrafenib twice daily and 2 mg of oral trametinib once daily until disease progression or intolerance of treatment. The primary end point was overall response rate (ORR). Median follow-up was 10 months (IQR 6-15).

In the trial, the combination therapy achieved an ORR of 51% (95% CI, 36-67) according to investigator assessments. The median duration of response was 8.7 months, with 7 patients seeing an ongoing response beyond 12 months. Moreover, median progression-free survival (PFS) was 9.1 months and median overall survival (OS) was 13.5 months, with 56.4% and 35.8% of patients still alive at 12 months and 24 months, respectively.

With regard to safety, all patients experienced at least 1 adverse event (AE), with the most common being fever, nausea, vomiting, diarrhea and fatigue. The most common grade 3 or worse AE was increased γ-glutamyltransferase in 5 (12%) patients. Further, 17 (40%) patients had serious AEs and 9 (21%) had treatment-related serious AEs, the most frequent being pyrexia (8 [19%]). Importantly though, no treatment-related deaths were reported.

Notably, the researchers indicated that these exploratory biomarker findings need to be validated in a larger study.

“The trajectory of cholangiocarcinoma is changing rapidly,” said co-author Milind Javle, MD, professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, said in the release. “Targeted therapy has made meaningful inroads, and this study is an excellent example of that. This is an important development for patients with cholangiocarcinoma and BRAF V600E mutations, who often have limited treatment options.”


1. 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. The Lancet Oncology. doi: 10.1016/S1470-2045(20)30321-1

2. Targeted therapy combination effective for patients with advanced cholangiocarcinoma and BRAF mutations [news release]. Houston. Published August 17, 2020. Accessed August 17, 2020.

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