Dr Amit Singal on the Improving Outlook for HCC and How to Choose Treatments

Amit Singal, MD, medical director of the Liver Tumor Program and chief of hepatology at UT Southwestern Medical Center, explained how the outlook for patients with hepatocellular carcinoma has changed in light of recent developments in immunotherapies and combination regimens.

Singal also discussed the nuances of choosing the best therapy regimen for patients with hepatocellular carcinoma.

How has the outlook for patients with hepatocellular carcinoma changed in the era of combination and immunotherapies?

I have to say it's an exciting time for patients with HCC because we've seen a lot of advances. From the systemic therapy landscape, we now see the introduction of immune checkpoint inhibitor combinations, which have significantly improved the median survival for these patients, now extending up from around 11 months all the way up to 19 to 22 months with the newest combinations that we have. This sort of favorable response and favorable survival in the advanced stage setting has now reignited enthusiasm for evaluating these immune checkpoint inhibitors even in earlier stages of disease—for example, looking at this in patients at high risk of recurrence after surgical resection in the adjuvant setting, and now even in the neoadjuvant setting, and so trials are ongoing in that setting. And then also looking at this in combination with locoregional therapies like chemoembolization or radioembolization to improve progression-free survival and overall survival.

I think, in general, we've seen significant improvement in outcomes, responses, progression-free survival, and overall survival for patients across the board, given the introduction of immune checkpoint inhibitors in the therapeutic landscape.

With guidelines recommending a range of systemic therapies, how do you discern which regimen has the most potential for a given patient?

With the progress that we've seen, I think it's brought about new questions. We now have multiple immune checkpoint inhibitor combinations that we can choose between in the advanced stage setting, and one of the common questions is how do you choose an individual therapy regimen for your patient sitting in front of you?

Unfortunately, there is no simple answer. I can't say, "Oh, this therapy is always the best for this individual patient, and this therapy should be used always in this other patient." I think it comes down to being seen in the right center, where you can actually take into account several of the different factors in terms of what is the best therapy for each individual patient. I think when you take a look at some of the differences, we do have, for example, atezolizumab plus bevacizumab, which is a combination of a PD-L1 and a VEGF inhibitor. And then we also have tremelimumab plus durvalumab, a CTLA4 in combination with a PD-L1.

Even though there's immune checkpoint inhibitor therapies for both of those different choices, the big difference is that we have a VEGF inhibitor in the former, the atezo-bev, and not in the latter. And we know that VEGF therapy can be associated with some potential AEs [adverse events]—for example, a higher risk of GI [gastrointestinal] bleeding, and some risk in patients with underlying cardiac dysfunction or history of stroke. And so, when we think through those different comorbidities or the risk of GI bleeding, that may make you lean more towards the latter choice, this durvalumab plus tremelimumab. So, you know, you have a sort of, quote unquote, contraindication to VEGF therapy or the bevacizumab. Short of having that contraindication, once again, I think it's more so thinking through small differences in the regimens, and then a discussion with the patient in front of you.