Ghassan K. Abou-Alfa, MD, MBA, FASCO, and Lorenza Rimassa, MD, on Unresectable Hepatocellular Carcinoma: 5-Year Overall Survival Results From the HIMALAYA Trial

Ghassan Abou-Alfa: Dr. Rimassa, Lorenza, I mean excited times with the HIMALAYA study. As we all know, this was the study that was phase III clinical trial, the largest ever clinical trial in primary liver cancer, HCC first-line systemic therapy looking into durvalumab plus tremelimumab versus sorafenib with positive outcome data that we were both part of and already we published and available and now also approved by the agencies. However, today we're talking about a further update on the data that you are sharing with us. What's the update on the survival? Lorenza Rimassa: Well, thank you Ghassan, Dr. Abou-Alfa. The updated survival presented the data at five years, and we have unprecedented data with 20% of patients alive at five years. So this means that 1 out of 5 patients with advanced or unresectable HCC is alive at five years. This is real important because we had a prior update at four years, and with this further update, we keep showing that the long-term survival is maintained with STRIDE. And this is really unique of this regimen. Another important thing is that we observed that the classical objective response, according to RECIST 1.1, it's not necessary to have long-term survival. Ghassan Abou-Alfa: Well, that's superb, Lorenza. I totally agree with you. And if anything, as you nicely presented to us, the 20% is compared only to about less than 10% on the sorafenib arm at five years. And if anything, it's a reminder for us about how important it is to do landmark analyses as we continue to benefit from the use of the checkpoint inhibitors in regard to HCC. A year ago we did present before the landmark at four years, at three years, and now, wow, at five years, as you said, with 20% of the patient still alive. So with this said, as you know, we're delighted to see this, but would like to also see it from the perspective that patients always like to ask about, which number one, is it safe? What's the update? Anything? Are there more side effects now with the longer survival? Your data on the update on the adverse events. Lorenza Rimassa: This is another important point. At five years we didn't observe any new serious adverse events, so the safety analysis showed the same serious adverse events at the primary analysis and at the updated five years. So it's important to point out that the safety profile doesn't change at five years. Ghassan Abou-Alfa: Wow. Superb. So in other words, wow, five years, people can live, can keep going in life. They'll just come for one injection of durvalumab once a month and that's it. Incredible that we're able to really see that people are able to function with limited, as you said, adverse events as well. With this said, however, and go back to another point I got to response, which is part of what patients always ask about and we're always, of course, interested then, how did this improved survival translate regard to the responses that we saw in the study? Lorenza Rimassa: Yes. Again, a really important point, and this is something new shown with this updated five-year data. The classical objective response according to RECIST 1.1 is not needed to achieve long-term survival. So even smaller reduction in the tumor diameters, even smaller than 30%, can be associated with long-term survival. We evaluated that the depth of response, of course, patients with deeper responses are more represented in the long-term survivors, but there are patients, as I was saying, with a small reduction in tumor diameters with long-term survival, with five years over survival. Ghassan Abou-Alfa: Incredible. So as we saw in the data, you have complete responses and you have quite a bit of robust partial responses. But please explain one more time for our colleagues what exactly you mean by depth of response. Lorenza Rimassa: This is an important point shown before in other cancer types, like for instance, melanoma. We have patients with a stable disease according to RECIST 1.1, and in the stable disease we have patients with different percentage of tumor reduction and patients with a small tumor reduction that doesn't qualify for objective response may, in any case, have a long-term survival. So this is really important because in some cases, for instance, with the STRIDE that we saw in the primary analysis, 20% response rate. But it's not that only those 20% of patients may have long-term survival. Also, patients with a stable disease, and even patients with initial disease progression and then stable disease and then maybe a reduction in tumor diameters, may have long-term survival. So this is another point that is very important to highlight. Ghassan Abou-Alfa: I totally agree. This is incredible that we are seeing here as we summarized, a five-year survival 20% with patients on the durvalumab-tremelimumab or the STRIDE regimen part of the HIMALAYA study. And this compared to less than 10% on sorafenib. Number two is no change at all in regards to the adverse events, and still broadly a very robust response panel, including even presence of CRs and a quite impressive continued PR with depths of the response as well.