Patient Factors Drive IO Combination Selection in Unresectable HCC

The first-line treatment field for patients with hepatocellular carcinoma (HCC) landscape has evolved in recent years with the addition of immunotherapy-based combination options, according to Aparna Parikh, MD, highlighting the FDA approvals of both atezolizumab (Tecentriq) plus bevacizumab (Avastin) and durvalumab (Imfinzi) plus tremelimumab (Imjudo).

Parikh, an associate professor of medicine at Harvard Medical School, and an assistant in Medicine, Hematology, and Oncology at Massachusetts General Hospital, in Boston, Massachusetts, sat down for an interview with OncLive® following a State of the Science Summit™ on gastrointestinal (GI) cancer, which she chaired, to discuss the current treatment landscape for HCC.

She also serves as an attending oncologist in the Tucker Gosnell Center for Gastrointestinal Cancers and the Henri and Belinda Termeer Center for Targeted Therapies.

Want to hear more from Dr Parikh? Check out our previous article, in which she delves into even more happenings in the GI cancer space, specifically focusing on the current treatment landscape of colorectal cancer and the use of novel agents.

OncLive: What are the immunotherapy options currently available for patients with Child-Pugh A unresectable HCC?

Parikh: Over the last several years, we've seen a change in the landscape [for unresectable HCC] with immunotherapies now being available for patients in the first line. All the clinical trials have looked at patients [with a] Child-Pugh A [score]. We touched on a couple of different options for HCC [during the State of the Science Summit]. The first option we talked about was atezolizumab plus bevacizumab, and the second option we talked about was durvalumab plus tremelimumab option.

With both immunotherapy-based combinations approved in the first-line setting, what influences treatment decisions for this patient population?

It is hard to know [which combination is better, as there has] never been a head-to-head trial [comparing atezolizumab plus bevacizumab vs durvalumab plus tremelimumab], and nor will there be. Therefore, it can be a little bit tricky to know which therapy should be selected for individual patients. Clinically, the lion's share of patients are [more likely going to be treated with] atezolizumab and bevacizumab.

The challenging thing with bevacizumab is that there is a risk of bleeding. [This is especially prevalent] in patients that have untreated or active varices, or have not had a chance to get an endoscopy. Those may be the patients who are more appropriate [to give] durvalumab plus tremelimumab.

What are your thoughts on the current clinical trial data for durvalumab plus lenvatinib (Lenvima) in unresectable HCC?

It's hard to think of a scenario where a patient would be eligible for durvalumab plus lenvatinib [without being] eligible for either atezolizumab plus bevacizumab or durvalumab plus tremelimumab. [Lenvatinib] is an oral option, which is a pro; [however], in terms of adverse effect [AE] profiles, lenvatinib does come with its own slew of AEs.

Performance status–wise and Child-Pugh status–wise, [durvalumab plus lenvatinib has been evaluated in] a similar bucket of patients, so it's hard for me to clinically see a case for why we would be using the lenvatinib/durvalumab option in the first line vs our other standard atezolizumab plus bevacizumab or durvalumab plus tremelimumab first-line options.