Second-Line Therapy for Advanced HCC: The RESOURCE Trial

Transcript: Andrew Zhu, MD, PhD: Even though we have the active systemic treatment, we know that these treatment regimens don’t have benefit forever. Eventually, patients will progress after the first-line treatment. I think when we had only 1 drug, sorafenib, when patients progressed, we had nothing to offer to those patients. But I think luckily in the last 2 to 3 years, we have actually quite a few active agents available. This is definitely bringing our patients a lot of other treatment options. Tell us, what do we have right now in the second-line or even third-line setting?

Nikolaos Pyrsopoulos, MD, PhD: That’s so exciting because 4, 5 years ago, unfortunately we were going back into the future. After sorafenib, people were giving systemic chemotherapy because they didn’t get more drugs to offer and patients were getting desperate. But suddenly we have this publication in Lancet Oncology that another multi—tyrosine kinase inhibitor with the name of regorafenib had been tested in more than 500 patients. This was a very nicely designed trial: double-blind, randomized control, multicenter. The overall survival rate appeared to be very promising. It was 10.6 months in patients who have tried sorafenib and couldn’t tolerate it or who broke through. And it was very appealing regarding the progression-free survival as well. It was approximately 5.5 months. In the control group, it was roughly 2 months.

Regarding the adverse-event profile—of course this is a compound similar to sorafenib—is similar to sorafenib. But there was a second publication that came after that tried to have a second cut and reevaluate a secondary point of analysis. And what came about was that regardless of the last dose of sorafenib or the time to progression with sorafenib, regorafenib was very effective. And if we try to put 1 plus 1, this turns out to be 26 months of survival while the patient was still on the trial, and this was the cut point. Suddenly, from a few months of survival back in the 1970s for these patients, now we are discussing almost 2 years.

Andrew Zhu, MD, PhD: Right. I think that study that you mentioned clearly illustrates, as we provide more treatment options for our patients, potentially a survival benefit will be improving. Clearly, there are some selection biases using the sorafenib followed by regorafenib sequencing. Nevertheless, that study does suggest if you apply the right sequencing, patient survival outcome may be actually improving. I think it’s really worth mentioning that in the RESORCE trial, they actually took patients who tolerated sorafenib but eventually progressed, and the study did not actually allow patients who could tolerate the sorafenib, which I think is really 1 of the key features for that study design.

Transcript Edited for Clarity