Hepatocellular Carcinoma - Episode 12

Case 4: Next-Generation Sequencing


Ghassan Abou-Alfa, MD, MBA:Interestingly, another category of drugs that is quite intriguing is theFGFRfusion—targeted agents. Let me ask again 1 more time, Farshid. Tell us a little more aboutFGFR. Are we looking for a fusion or a mutation? Which one?

Farshid Dayyani, MD:I think we are looking more for fusion rather than mutations in cholangiocarcinoma. And the data that we have show that mutations probably don’t work as well from other solid tumors than alterations that we look for. We have 2 agents that have been observed in relatively large single-arm trials with high response rates in the 25% to 35% range and, importantly, high disease-control rates in the 75% to 85% range with infigratinib and pemigatinib recently. Those will be validated, I think, in larger phase III trials.FGFR2historically seems to be maybe favorable prognostic factor in intrahepatic disease, but I think now it becomes more of a predictive factor, especially as fusions are detected by NGS [next-generation sequencing].

Ghassan Abou-Alfa, MD, MBA:I totally agree. If anything, there are quite a bit of intriguing trials. As you mentioned, the infigratinib and pemigatinib are actually being looked into first line versus gemcitabine and cisplatin as the standard of care, exactly as Farshid already mentioned to us. Interestingly, there is a crossover prospective, and we’ll see where these might define or decide where the anti-FGFR2fusions will come into play. Nonetheless, there are other agents that really are being looked at, among which are debio 1347, TAS-120, etc. We are trying to understand better where they will take us.

Interestingly, if anything, the message over here is that despite nothing yet being approved by the FDA, at least we have the MSI-high strategy, which is enough suggestion for our patients to make sure that we do the next-generation sequencing for all those patients. That brings up a very important point, and I’ll go back to Riad over here. When do we get the next-generation sequencing? Do we wait until the patient needs a systemic therapy, or should we do it from the start? Is this on your mind-set as an interventional radiologist, or would you like to pass on a message to your colleagues in interventional radiology?

Riad Salem, MD:I can address the tactical issues that exist with that. Certainly, based on where the lesions are, these are things that we can get up front. There’s no doubt that we are in a world in which biopsying up front and actually after treatment looking for mutations is something that we’re seeing. Now the oncology practice and interventional radiology have become very biopsy heavy because of the advent of all these agents. For me it seems like it starts certainly up front as a baseline biopsy, but certainly there’s no doubt that that continues to increase. As you’re switching classes of agents and types of treatments, there’s no doubt that the number of biopsies is increasing, and this is something that clearly we’re able to do in interventional radiology.

Ghassan Abou-Alfa, MD, MBA:I totally agree with Riad. This is our message and our obligation to talk to all our colleagues. One more time, we revisit the multidisciplinary approach. When we have somebody who is going for a surgery or going for a local therapy, we would like to make sure that a piece of the tissue is removed at surgery, or a biopsy at the time of the local therapy, or even an intervention such as a biliary drain. That’s needed to make sure you get tissue, so we can get the diagnosis established for next-generation sequencing. Because obviously this might take a little bit of time, and having these data ahead of time can really save a lot of time for the patients to get on the correct clinical trial and be treated accordingly—in no time, hopefully, because we need to make sure we add more options for our patients in regard to therapy. We will see those drugs really prove their point in regard to treatment.

Transcript edited for clarity.