Ghassan K. Abou-Alfa, MD, MBA, FASCO, and Lorenza Rimassa, MD, on Doublet Immunotherapy Options for Unresectable Hepatocellular Carcinoma

Ghassan Abou-Alfa: No doubt we're very grateful for the opportunity that we had at ESMO to present that data and delighted that you presented on behalf of all of us. But of course, this comes at that point where we have the new therapy, the ipilimumab plus nivolumab that were just brought in. Why our colleagues should choose this or that? Your thoughts. Lorenza Rimassa: This is a difficult question, but I think we have data from HIMALAYA, we have data for many several years up now. The first data were presented a couple of years ago, we have a published primary analysis paper, we have a publication with the four-year update. Now we have the data at five years. So the data are really mature. We have several data. Now, as mentioned, we are evaluating also different response measures. So I think the data are more complete and we can be more comfortable in telling also this data to our patients and using the data in clinical practice. Ghassan Abou-Alfa: I totally agree and I like that very much. I love the way you said it because, to be fair, we have mature data. Ipi-Nivo is a new kid on the block. I want to call it that way. To be fair, we have to really present justice here regard to how much we know about one study versus the other. However, interestingly, one kind of intriguing point that really still kind of leaves us with bit of unease, the empowerment of a one dose of the tremelimumab with the 300 milligram given only one time in patient's lifetime compared to the four doses of the Ipi, and if you recall, and maybe you can tell our colleagues the four doses kind of thing with the Treme, we did it before part of the phase II study. Tell us about what did we see there? Lorenza Rimassa: Yeah, we did it in the study 22. What we saw that the efficacy was not so good, as in with the STRIDE regimen with a single primary dose of tremelimumab, and also the safety profile was not so good. For instance, with STRIDE, we observe that only 20% of the patients required the high-dose steroids to manage immune-mediated adverse events. With the other double immunotherapy combinations, this percentage is higher, and we know that especially in patients with liver cirrhosis, we don't like to administer high-dose steroids. So I think the safety profile with a single dose of tremelimumab is very good. Ghassan Abou-Alfa: I totally agree, and to be fair, we'll just have to wait for more data on this. But as everybody knows, actually the HIMALAYA study had an arm of the four doses of the tremelimumab at 75 milligram each. And as Dr. Rimassa said, because of the [inaudible 00:09:05] 22, we did not see any difference in outcome compared to durvalumab as single agent. This arm was discontinued and we kept on with the only 300 milligram of tremelimumab as well. So to be fair, we have to wait and see more data, but nonetheless, still we're delighted, and on behalf of all our colleagues were delighted and honored to have really led this important effort, the HIMALAYA study, which remains the largest study in liver cancer now with 20% five-year survival, with still a very well-maintained, no change at all, no worsening, especially regard to the adverse events, and broadly was also continued benefit with responses including CRs and robust PR and the depth of response. Thank you very much.