VIDEO: Emergence of targeted therapies ‘broadened treatment options’ for cholangiocarcinoma

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

Prior to this era of precision medicine which ushered in multiple targeted therapies, the systemic therapy treatment options for patients with cholangiocarcinoma were quite limited and not very effective. And so, the emergence of targeted therapies has, without a doubt, broadened treatment options for our patients. Approximately 40 to 50% of patients with intrahepatic carcinoma, so there are three different subtypes of cholangiocarcinoma, and one of those is intrahepatic carcinoma, so approximately 40 to 50% of these patients have actionable genetic alterations, meaning, genetic abnormality in their tumor that can potentially be targeted. The other two main subtypes of cholangiocarcinoma are distal or perihilar cholangiocarcinoma, and these subtypes are based on the location of the tumor within the biliary tract. And so, for patients with distal or perihilar cholangiocarcinoma, approximately 15 to 20% of those patients have actionable genetic alterations. So there are several different targeted treatment options for these subset of cholangiocarcinoma locations who harbor certain genetic alterations or abnormalities. For instance, these include fibroblast growth factor receptor 2, or FGFR two, gene fusions, and-or, alterations. FGFR2 gene fusions are present in approximately 15% of patients with intrahepatic cholangiocarcinoma, they're not as commonly seen in patients with distal or perihilar cholangiocarcinoma. And in terms of therapies against these FGFR2 alterations, there are now FGFR2 inhibitors that have received FDA approval, and these include pemigatnib which was the first FGFR2 inhibitor that was FDA approved. And more recently the FDA approved futibatnib, and futibatnib is a next generation inhibitor that has the potential to overcome acquired resistance to the earlier FGFR inhibitors like pemigatnib. Another type of genetic alteration that we see in patients, again, this is primarily in patients with intrahepatic cholangiocarcinoma, are isocitrate dehydrogenase or IDH mutations. And so, IDH inhibitors are another targeted therapy available for cholangiocarcinoma patients, and of the IDH1 inhibitor ivosidenib has received FDA approval for the treatment of IDH1-mutated cholangiocarcinoma. But there are multiple other IDH inhibitors that are currently under investigation in a variety of clinical trials. Another type of alteration that we see, and this is in a much smaller subset of cholangiocarcinoma patients, approximately 5% of patients with cholangiocarcinoma have BRAF mutation. And there are inhibitors that have been evaluated, and there's one particular combination, the combination of a BRAF inhibitor debrafenib and the MEK inhibitor trametinib, which was approved by the FDA for treatment of non-colorectal solid tumors, which includes cholangiocarcinoma, and these solid tumors that are harboring this BRAF mutation. So again, all of these are targeted therapies applicable solely to patients who have those respective genetic mutations. And unlike FGFR2 alterations and IDH mutations, which I said are much more common in patients with intrahepatic cholangiocarcinoma, HER2 overexpression is more commonly seen in perihilar and distal cholangiocarcinoma compared to intrahepatic. And there are several HER2 targeting antibodies that are currently under investigation in different clinical trials. And so, I think there's a lot on the horizon. There are multiple clinical trials that are currently ongoing to assess a myriad of different systemic treatment options. So these include targeted therapies, some of these I have outlined, there are immunotherapies, there are trials that are looking at the combination of targeted and immunotherapies, and also conventional sort of cytotoxic chemotherapies. And so, we eagerly await the results of these trials, and so, as I said, I think there's a great deal on the horizon which does offer hope to our patients and their families.