Clinical Relevance of BRAF Alterations in Biliary Tract Cancers

Preliminary Results From the B-REAL Study

At the 2023 World Congress on Gastrointestinal Cancers, Monica Niger, MD, National Cancer Institute of Milan, Italy, shares results from a study investigating the clinical relevance of BRAF alterations among patients with advanced biliary tract cancers.

Dr Niger concluded, “BRAF is confirmed to be a biomarker that we should work into, and that the clinical activity of these inhibitors is confirmed" for advanced biliary tract cancer, adding, “we have to work a little bit more into finding enough BRAF-altered patients with non-V600E mutations to actually understand how this subset of patients respond to therapies and find the right strategy to target them."

Transcript:

I am Monica Niger from the National Cancer Institute of Milan, Italy, and my abstract was an observational study on BRAF alterations in biliary tract cancers (BTC). As we all know, biliary tract cancer is a group of diseases with a very aggressive attitude, poor outcomes, and limited therapeutic options. We have more and more data regarding molecular targets in this kind of disease, and BRAF alterations are emerging as one of the most relevant biomarkers there is for this disease. We know that BRAF mutations can be grouped in class I, II, and III according to their kinase activity and RAS dependency. Class I is the most known of, with BRAF-V600, BRAF-V600E mainly, as the most common and used in the clinic due to the fact that we have BRAF-inhibitors working in many tumor types.

We have only dabrafenib and trametinib approved by FDA for all solid tumors bearing this alteration, including BTC, but biliary tract cancers are rare and the trials using dabrafenib/trametinib enrolled less than 50 patients, so we needed more data from real life, and this is where our study comes into the scene. We had a study conducted at 5 Italian institutions evaluating the molecular characteristics of this subset of patients, the clinical characteristics of patients with BRAF alterations, and the impact of these mutations into the outcomes overall and the progression-free survival (PFS) to first-line chemotherapy. We looked at all the clinical data of patients we knew the BRAF status on. We enrolled 628 patients and we found BRAF alteration in 29 of them, so it is a little bit less than 5% of patients.

Half of those patients, roughly, had BRAF class I mutation, BRAF-V600E mainly, and the other half had BRAF non-V600E mutation. We didn't find any significant difference in terms of overall survival or PFS to first-line chemotherapy. We did see the trend toward worse outcome for BRAF non-V600E mutation, so that's something we will probably look into with a number of patients, in order to have more information.

We think that BRAF is confirmed to be a biomarker that we should work into, and that the clinical activity of these inhibitors is confirmed, since we had 9 patients treated with BRAF inhibitors, with or without MEK inhibitors, and they had a decent outcome because they were heavily pre-treated, and we got a PFS of roughly the same, 7 months, and a median OS of 9 months. We think that we have to work a little bit more into finding enough BRAF-altered patients with non-V600E mutations to actually understand how this subset of patients respond to therapies and find the right strategy to target them. Thank you for your attention.

Source:

Niger M, Nichetti F, Murgioni S, et al. Clinical relevance and actionability of BRAF alterations in advanced biliary tract cancer: Preliminary results from the multicenter B-REAL study. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-3