Sorafenib Plus SBRT Improves Survival in Advanced HCC

In this exclusive roundtable video from MedPage Today, three expert leaders in the field of gastrointestinal cancer discuss the latest data presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

Moderator Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, is joined by Anthony B. El-Khoueiry, MD, of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and Steven Maron, MD, MSc, also of Memorial Sloan Kettering Cancer Center, in this last of four episodes, in which they discuss the phase III NRG/RTOG 1112 trial.

Following is a transcript of their remarks:

Abou-Alfa: Well, hello everybody, and great seeing you again. And whoa, we are still kind of wrapping up from GI ASCO, and still going on with a lot of information that we thought, why not have a roundtable and discuss some of the new things that were evolving. We learned from each other, a lot of things that we learned and a lot of things that we reflected on.

So, as you know, my name is Ghassan Abou-Alfa from Memorial Sloan Kettering Cancer Center in New York. And today I would like to welcome my two dear colleagues, Dr. Anthony El-Khoueiry from the University of Southern California Norris Cancer Center, and Dr. Steve Maron, dear colleague, also from Memorial Sloan Kettering Cancer Center in New York.

So let’s start to switch gears because, it’s amazing, you and I lived it from the start and look where we are now. And interestingly now we’re talking about radiation therapy for liver cancer. So tell us the whole story of the NRG study.

El-Khoueiry: Yeah, so this is an NRG/RTOG 1112 [study] presented by Laura Dawson, and it was really the first phase III trial to look at the benefit of stereotactic body radiotherapy, so SBRT, in patients with advanced HCC. So there had been a lot of early data from phase I and II trials suggesting that SBRT is beneficial, especially in patients who have a vascular invasion, portal vein tumor thrombosis. So this is what RTOG 1112 was built on. And Ghassan, you had a big role in allowing that study to be conducted through the National Clinical Trials Network, the cooperative groups, and making sure that we get it done.

So the study randomized patients to the standard at that time, which was sorafenib [Nexavar] versus SBRT, followed by sorafenib. And there was a limit on the total tumor burden in the liver. So not greater than 20 centimeters, I think, total diameters of lesions. And patients were definitely allowed to have vascular invasion. If they had extrahepatic disease, they had to be less than 3 centimeters.

And when you look at the patients that were recruited to that trial, the majority were patients with vascular invasion. And the majority because of that were BCLC [Barcelona Clinic Liver Cancer] stage C patients. Of course, all of them were Child-Pugh A, and I would say these are the important characteristics to remember.

Now, the study had slow accrual, which led to changes in the statistics. So the power, because of the reduced total accrual of the study, the power went down to around I believe 65 instead of 80-90% power. But with that reduction, the study did show an improvement in both overall survival and PFS [progression-free survival] with the addition of SBRT to sorafenib in that patient population.

The median OS [overall survival] with this SBRT sorafenib combo was 15.3 months or so. So, not very far off if we do a cross trial comparison from using single agent PD-1, let’s say, in those patients.

So there were some concerns that the confidence interval just crossed one and the P-value was 0.055, not quite below 0.05. But the body of the data — because there was improvement in OS, in PFS in response, it was tolerable, it was feasible, and this is a tough population, majority vascular invasion — I do think it does establish a role for SBRT in select patients. And I think the next step, like Dr. Dawson said, to evaluate this in the context of modern regimens will be very important. So it’s a tough study to discuss, but that’s my take on it.

Abou-Alfa: Beautifully said, and I totally concur on all of what you said, and this is the reality that we live in. We saw it with Dr. Maron, we saw it with Dr. El-Khoueiry, that after all this is a very dynamic field. It’s not like I’m going to do a study and everything’s going to remain quiet until I get the results of my study. Things are moving very quickly; enough that, for example, as we just heard, in the RTOG study the comparison was sorafenib, which is not really what we use nowadays anymore, per se, with the advent of new therapies. And really, I give a lot of credit for Laura Dawson that she brought it, I remember her very clearly, she said that it’s time to really look into comparison to the novel approaches, including the checkpoint inhibitors, and that’s the dynamism that will come from those studies. And you’re right, thanks for your acknowledgement of the effort.

Of course, when I was chairing the task force, I’ll tell you both studies the 1812 and the NRG, was like the encouragement and the support. But I have to say we have a great, great team being in gastric or in hepatobiliary that always our people are ready to help any way they can to help our patients per se.

We heard a lot from both Dr. Maron and Dr. El-Khoueiry. We heard especially about the Claudin 18.2 and zolbetuximab from Dr. Maron and also from Dr. El-Khoueiry. We maybe did not have the super-positive data, but nonetheless, we are still going in the right direction for an enhancement of the checkpoint inhibitors, and the perfect baseline combination that will get better care and therapy for our patients with HCC.

With this, we thank you very much for listening again and hopefully you’ll have a great day and hope we connect again soon.

Watch episode one: Two Biliary Tract Cancer Trials Took Center Stage at ASCO GI

Watch episode two: The Role of Checkpoint Inhibitors in Gastric Cancer

Watch episode three: Tislelizumab Plus Chemo for Advanced Gastric/GEJ Cancer