Hepatocellular Carcinoma: Future Role of Immunotherapy
Insights From: Ghassan Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center
Ghassan Abou-Alfa, MD: While we’re getting all those great results from checkpoint inhibitors, as we just discussed, you already have nivolumab onboard, you have pembrolizumab onboard, and you have durvalumab and tremelimumab in combination onboard especially. This is all great news. In addition to that, looking beyond systemic disease and into combinations for local therapy with any of those checkpoint inhibitors plus an actual local therapy like an embolization is, by all means, also looking forward.
However, a very important point is that we need to further dissect who is who in that whole story. While we said that any patient is technically eligible short of certain limitations in regard to checkpoint inhibitors, we also have to remember that we don’t know yet. We don’t have that sense about who really will respond best. Is it patient-based on gender? Is it based on ethnicity? Is it based on the etiology? Especially here, I talk about hepatitis B versus hepatitis C. We don’t have all those data yet.
The nice thing is that we are currently undergoing a major effort worldwide of collecting tissue from different cohorts of patients with liver cancer all over the world, and we’re trying to further dissect what it means to be a patient from one specific cohort versus another in regard to potential outcomes from the use of checkpoint inhibitors.
A question that I’m asked all the time is, how would we know if a patient might respond or how would you know if they have responded to checkpoint inhibitors, or immunotherapy? By all means, it will be rather difficult to expect who will respond because we don’t yet have that sense about certain markers in regard to who might be more able to respond. But on the other hand, how do we assess a response? The best option, no question, is to look at the imaging and look for the response as we all know it.
There are certain variants to that, including the iRECIST, which is a form of RECIST criteria for immunotherapy treatment. But it is more important to remember something about the potential for a pseudoprogression where, in other words, patients might see further growth in the tumor while they’re clinically doing great. As such, we have already been told that patients of that nature should continue in the therapy for at least another CAT scan and see if they respond or not. So, I would say an assessment for patients on a checkpoint inhibitor with HCC is multifactorial, and it’s a good idea to open the discussion back and forth with the different players in the game as part of a multidisciplinary team. It should not be as easy as saying it’s bigger, which means it’s not working; or it’s smaller, which means it’s working. There are certain variants one way or another.
This year, 2018, is really nothing more than a great continuation for the excellent story that we have listened to in 2017 as far as treatment for HCC. If anything, part of the long story are the TKIs that started with regorafenib in 2017, followed by lenvatinib in 2017, and now, in 2018, we’re going to talk at this meeting about cabozantinib. But there’s also a continued story for checkpoint inhibitors. That story started in 2017 with the approval of nivolumab, but at the moment I think the biggest 2 stories probably include 1 that is already wrapping up its final stage, which is nivolumab versus sorafenib. But a very important study is the HIMALAYA study, which is looking at the combination of durvalumab plus tremelimumab, versus durvalumab, versus tremelimumab, versus sorafenib. So, there’s quite a bit going on, and we look very much forward to seeing how these trials will end up.