Etiology Plays Role in Outcomes of Frontline HCC Trials

Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the significance of disease etiology when exploring the results of recent trials of patients with unresectable hepatocellular carcinoma (HCC).

Abou-Alfa says that studies of new regimens have included varying proportions of patients with hepatitis B etiology, which can be explained by geographic location of these studiesand could influence their outcomes. The IMbrave150 trial (NCT03434379) of the combination of bevacizumab (Avastin) plus atezolizumab (Tecentriq) had 49% with hepatitis B etiology, and real-world data on this combination had under 40% with hepatitis B etiology. The LEAP-002 (NCT03713593) trial of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) had approximately 50% of patients with this etiology.

Abou-Alfa notes that the China-based phase 3 trial (NCT03764293) investigating camrelizumab (SHR-1210) plus rivoceranib had approximately 75% hepatitis B etiology patient population, and this population could contribute to the favorable efficacy in the trial.

Finally, the HIMALAYA trial (NCT03298451), which led to the approval of durvalumab (Imfinzi) plus tremelimumab (Imjudo) had approximately 30% with hepatitis B, 30% with hepatitis C, and 40% with nonviral etiology. Abou-Alfa says that this global study, which is the largest in this setting with 1400 patients, is a good reference point based on its representation of disease etiologies. He says it may become necessary to conduct trials based on etiology to distinguish its impact on treatment efficacy, or further study the immune microenvironment to see what variables lead to different outcomes with immunotherapy in HCC.

TRANSCRIPTION:

0:08 | What is the key element here? I would say it's probably all about the etiology. No. 1: in the real-world data from the atezolizumab plus bevacizumab, there were less than 50% of patients of the IMbrave150 that were positive for hepatitis B. No. 2 is the very robust results that we have seen for the camrelizumab plus rivoceranib is dependent on 75% of the patients with hepatitis B and to add to this, 50% of the patients had hepatitis B in regard to the lenvatinib plus pembrolizumab. Interestingly, in the real-world data, however, the percentage with hepatitis B was only about 30% to 40%. Interestingly, the same thing applies for the patients in the HIMALAYA study, which was only 30%.

0:56 | Clearly, etiology does play a role, and you can get more benefit here and there. Could it be that now the future is that, No. 1, we have a dynamic field and we have to settle for what would be a good reference point for us? I would say, as an example, durvalumab/tremelimumab because it's a global study with 1400 patients; it’s the largest study ever. At the same time, it includes 30% with hepatitis B, 30% with hepatitis C, and 40% non-viral, probably a good representation. No. 2, could it be that we have to start delineating the patients based on the specific etiology and do different trials? Time will tell. No. 3…the immune microenvironment with other variables could be analyzed, and of course, this is [something] to think of as well.