Cholangiocarcinoma Linked to BRAF V600 Responds to Dual Drug Combo

According to a publication from CURE Magazine, in a phase 2 clinical trial nearly 50% of patients with a certain type of cholangiocarcinoma responded to a treatment comprised of two drugs, dabrafenib (marketed as Tafinlar) and trametinib (marketed as Mekinist).

About Cholangiocarcinoma

Cholangiocarcinoma is type of cancer that forms in the bile ducts that link the liver to the gallbladder and small intestine. Bile is a liquid produced by the liver that plays a crucial role in digestion.

It’s a relatively rare form of cancer that occurs mostly in those over 50. Doctors categorize the disease into three types – intrahepatic, hilar, and distal, depending on the portion of bile duct that is affected. Intraheptic bile ducts are small ducts in the liver itself, hilar cholangiocarcinoma affects the bile ducts that lead out of the liver, and distal cholangiocarcinoma affects the duct nearest the small intestine.

About the Phase 2 Trial

The trial involved 35 participants with advanced cholangiocarcinoma linked to a specific mutation of a gene called BRAF. Participants with the mutation called BRAF V600 were treated with a combination of the drugs Tafinlar and Mekinist (which inhibit the genes BRAF and MEK, involved in protein encoding). The BRAF V600 mutation is associated with up to 20% of cholangiocarcinoma cases.

The dual drug combination was later associated with a 42% response rate in the respondents – defined as patients whose tumors either shrunk or held at the same size. The therapy also yielded a median overall survival of 11.7 months.

These numbers represent a serious improvement in the prognosis of cholangiocarcinoma patients, many of whom are at an advanced age.

However, that’s not to say that the trial didn’t have its risks. At the time results were recorded, 22 patients had, at some point during the trial, delayed taking a dose of Tafinlar. Additionally, 21 patients had to delay taking Mekinist at some point. Typically, a delay in dosing was decided upon in the face of serious to severe side effects like fever (experienced by 40% of patients), rash (29%), nausea (23%), or more.

Dr. Zev Wainberg, co-director of the UCLA Gastrointestinal Oncology Program, noted that BRAF V600 is one of the few known driving mutations to be strongly linked to cholangiocarcinoma. He added that patients with bile tract cancers should be considered for routine screenings for BRAF V600 – especially since this combination therapy could one day be approved for their treatment.


What do you make of this exciting development? Do you think the potential side effects will prove to be a serious concern in further trials? Share your thoughts with Patient Worthy!

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