Ghassan K. Abou-Alfa, MD, PhD, FASCO, on Unresectable Embolization-Eligible HCC: Efficacy and Safety Data From EMERALD-3

EMERALD-3 was an expected and looked-forward-to study because, for the first time, for the most commonly used therapy in liver cancer, which is chemoembolization, we're trying to see if we can empower it further by adding on immunotherapy. Why would you do that? Because, understandably, when you do the embolization, you release antigens, which really will be an opportunity for enhancing the activity of the immune checkpoints. And there's such an opportunity for us to apply checkpoint inhibitors like anti–PD-L1, which is durvalumab in our example. And added to this, it can be enhanced further by anti-VEGF, where our example was lenvatinib. And of course, most importantly, we're really covering all of that from the top of this chain of command, which is anti–CTLA-4, with tremelimumab. As far as the study was to look into tremelimumab plus durvalumab, which we call the STRIDE regimen, as you know, plus lenvatinib plus chemoembolization, or TACE, and arm B was STRIDE again plus TACE, and arm C was TACE. The primary endpoint was to look at STRIDE, lenvatinib, and TACE compared with TACE alone. But of course, we looked at everything else because PFS was the primary endpoint, but we took it to OS, reported PFS for arm B as well, etc. This study showed an impressive improvement in outcome in regard to the PFS for arm A versus arm C. And even though we were able to report the data on all 4 parts of the study, being PFS for A versus C, PFS for B versus C, OS for A versus C, and OS for B versus C, however, it was not formally analyzed because we're waiting for any hierarchical kind of order, waiting for the maturity of each one of those steps. And as such, the overall survival, which was critical, showed an improvement in outcome in favor of both the STRIDE, lenvatinib, and TACE and also in favor of the STRIDE plus TACE. We were intrigued, and I'm so happy and I'm so thankful for all colleagues who asked, like, what about A versus B, which was really good news. We preplanned it, and we did report that as well. We're now comparing STRIDE plus lenvatinib plus TACE versus STRIDE plus TACE. And we found out that really adding on or not adding on the lenvatinib did not matter much, ie, we can say that it stands here for us, probably, will be the STRIDE plus TACE. One caveat. Interestingly, for only the population who are from Japan and also for the nonviral, maybe it favored the lenvatinib addition added to the STRIDE plus TACE. Of course, more analysis would come and follow accordingly. Last point, in regard to adverse events, thankfully, we did not see anything of concern. The expected concerns that will bring in with embolization were there, specifically the postembolization syndrome, and add to this the classic standard that you can see some reporting of. But thankfully, nothing critically of grade 3 or 4 except for the hypertension, which was noted, of course, in the lenvatinib arm, arm A. I would say that, from the patient perspective, patient-reported outcomes are definitely valuable, and I think we'll definitely look forward to reporting all this information later. As you all know, if you didn't catch up on any of those details, the good news is it's already accepted and in press for The Lancet Oncology, and on behalf of all my colleagues, I'm delighted to report that information. And yes, everybody asked me, and this is very true. Tomorrow I'll be in clinic, and guess what standard-of-care therapy is going to be? STRIDE plus TACE.