Drug combo shows promise in bile duct cancer with mutations

Article written by Bruce Sylvester

Dabrafenib plus trametinib combination appears to be a promising treatment for patients with bile duct cancer (biliary tract cancer) with BRAF V600E mutations. Researchers reported these findings on August 17, 2020 in Lancet Oncology.

“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,” said investigator and  author Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston, Texas. “These findings also reinforce the need for routine testing of BRAF mutations in patients with biliary tract cancers,” he added.

Mutations in the BRAF gene appear in 5-7% of patients diagnosed with bile duct cancer. Such patients are more likely to have poor outcomes. While single-agent therapies targeting BRAF have shown efficacy for patients with these mutations, they have been associated with significant toxicities, including secondary malignancies.

This study is part of an ongoing Phase II efficacy and safety trial of this drug combination for subjects with a variety of BRAF V600E-mutated rare cancers.

For the bile duct cohort, the investigators enrolled 43 patients with unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, all of whom had already been treated with at least one therapy.

Median age was 57, and women were 56% of the cohort.

The investigators reported that subjects who received the combination therapy achieved an overall response rate of 51% (22 patients). The median duration of response was 8.7 months. Seven subjects achieved an ongoing response of more than 12 months.

Median progression-free survival was 9.1 months. Median overall survival was 13.5 months. And 56.4% of the subjects were alive at 12 months, 35.8% at 24 months.

All subjects reported at least one adverse event, most commonly fever, nausea, vomiting, diarrhea and fatigue. Twenty-four patients (56%) had a Grade 3 or 4 adverse event, most commonly an increase in gamma-glutamyltransferase, an enzyme found in the liver and bile ducts.

The side effects were similar to those appearing in other cancer trials of the drug combination. No treatment-related deaths were reported.

The authors concluded, “Dabrafenib plus trametinib combination treatment showed promising activity in patients with BRAF V600E-mutated biliary tract cancer, with a manageable safety profile. Routine testing for BRAF V600E mutations should be considered in patients with biliary tract cancer.”