Update on Systemic Therapy for Advanced Liver Cancer - Episode 1

Newly Diagnosed Advanced HCC: Frontline Therapy Overview

Transcript: Andrew Zhu, MD, PhD: Welcome to the OncLive® News Network. Today we’re going to discuss the systemic treatment landscape for advanced hepatocellular carcinoma. I’m Andrew Zhu, your host, from Massachusetts General Hospital in Boston, Massachusetts. Joining me today is my good colleague, Dr Nik Pyrsopoulos, a professor of medicine and the chief of hepatology and gastroenterology from Rutgers New Jersey Medical School. Welcome, Nik.

Nikolaos Pyrsopoulos, MD, PhD: Thank you for having me.

Andrew Zhu, MD, PhD: We’ll be spending the next 45 minutes discussing the evolving treatment landscape for advanced hepatocellular carcinoma and treatment selection for the first line as well as for the second line of treatment. I think this is really a very exciting field. I hope the audience will enjoy our program.

Nik, this is a very exciting field. We really have quite a few interesting drugs for the first line as well as for the second line of treatment. On the other hand, this has been going on for more than a decade. We have made a lot of progress in the past decade. Perhaps we can reflect on this a bit. In the current treatment era, what options do we have for first-line treatment right now for hepatocellular carcinoma, Nik?

Nikolaos Pyrsopoulos, MD, PhD: Andrew, thank you very much for having me. I’m really thrilled and honored to be joining you during the session. Undoubtedly, during the last 10 years, long strides have been made. If we look back, in 2006 we had the first announcement from the SHARP trial that this compound, which is a multikinase inhibitor with the name sorafenib, provided some signal that the survival was better than the placebo. We had the first publication back in 2008, though the medication was approved in November 2007. This is a multicenter international double-blind randomized controlled trial. Sorafenib was utilized in a number of patients and proven to be statistically significant in regard to the overall survival, which was 10.7 months, versus the placebo, which was 7.9 months.

Subsequently we had the first medication that was FDA approved. But there was a big void for the following 10 years. A number of trials, unfortunately, with medications such as erlotinib, did not pan out. Suddenly, a couple of years ago, we had this compound that was tested in an open-label trial in over 900 patients with the name Lenvima, which is another multikinase inhibitor, blocking some additional kinases that sorafenib perhaps is not like the FGF, the fibroblast growth factor. Although the trial has targeted noninferiority, it’s a positive trial, and we have 13.6 months overall survival.

Andrew Zhu, MD, PhD: Absolutely.

Nikolaos Pyrsopoulos, MD, PhD: Versus the sorafenib, which showed 12.4 months overall survival. That proved to be efficacious the way their initial registration trial was, and the adverse-event profile wasn’t bad at all for either medication.

Andrew Zhu, MD, PhD: Nik, you mentioned the REFLECT trial right there, so clearly after sorafenib we finally have a second drug as a first-line treatment option. Beyond these 2 targeted agents, Nik, traditionally we’ve been struggling so much. We’re trying to use chemotherapy; we’re using even locoregional therapy. Tell me whether you see still any value using chemotherapy in the first-line setting right now.

Nikolaos Pyrsopoulos, MD, PhD: That’s a very good question, because in some other areas of this world, these compounds may not available or very popular, and there might be some utilization of chemotherapy. But in general, according to our guidelines that have been published by the oncologist and hepatologist societies, I’m not sure if chemotherapy as systemic therapy has any role. On the contrary, for transarterial chemoembolization [TACE], as a part of locoregional therapy, absolutely there is a very valid implementation, especially for patients who are at an earlier stage. In other words, they’re not unresectable, for example. Of course, there is room for locoregional therapy to be implemented, like TACE, or transarterial radioembolization, microwave ablation, or radiofrequency ablation.

Andrew Zhu, MD, PhD: But I think the consensus is that if you really have disease that’s already beyond the liver, if you have metastatic disease, I think all of us will reach the consensus that systemic therapy should actually be the treatment modality that we should be considering.

Nikolaos Pyrsopoulos, MD, PhD: Absolutely.

Andrew Zhu, MD, PhD: That’s great, yes.

Nikolaos Pyrsoppulos, MD, PhD: We need to know when to pull the plug—instead of going on with locoregional therapies—and move toward the next step.

Transcript Edited for Clarity