Choosing Second-Line Therapy for HCC After Atezolizumab/Bevacizumab

Daneng Li, MD, associate professor in the Department of Medical Oncology & Therapeutics Research and hepatobiliary tumor lead at City of Hope, discusses potential second-line options following treatment with bevacizumab (Avastin) plus atezolizumab (Tecentriq) in patients with hepatocellular carcinoma (HCC).

Li says that atezolizumab/bevacizumab is the favored frontline treatment for most patients with HCC. There are limited data on what treatment is most effective after atezolizumab/bevacizumab.

The tyrosine kinase inhibitors sorafenib (Nexavar) and lenvatinib (Lenvima), which are also approved as first-line therapy, could be used in the second line. Another option is cabozantinib (Cabometyx) based on the randomized phase 3 CELESTIAL study (NCT01908426). CELESTIAL showed efficacy of cabozantinib over placebo in patients with HCC who had previously received sorafenib. Similarly, in the phase 3 RESORCE trial (NCT01774344), regorafenib (Stivarga) demonstrated benefit versus placebo in patients with HCC who had previously received sorafenib.

According to Li, lenvatinib is the strongest of these agents based on its higher objective response rate (ORR) of 24.1% as frontline therapy in the REFLECT trial (NCT01761266), which suggests patients would have more tumor shrinkage with this agent. Cabozantinib may be considered for some patients because the CELESTIAL trial had more open enrollment criteria including patients with main portal vein invasion as well as allowing patients who could not tolerate first-line therapy and those who had more than 1 prior line of therapy.

TRANSCRIPTION:

0:08 | Atezolizumab plus bevacizumab is the dominant frontline treatment for our patients with unresectable HCC. The question really becomes: what do you do after progression of disease after atezolizumab plus bevacizumab? And I think there [are] still really 2 trains of thought here. One idea is that you would essentially go to our prior first-line treatments that we used prior to the approval of atezolizumab plus bevacizumab, whether it's sorafenib or lenvatinib, and use those in a second-line setting post atezolizumab/bevacizumab. And then there's the other train of thought in terms of jumping specifically to the second-line agent with agents such as cabozantinib based off of the CELESTIAL phase 3 study, as well as regorafenib if they potentially tolerated sorafenib previously.

1:10 | I would say for me, in clinical practice, it's dependent on the 2 medications, whether it's lenvatinib or cabozantinib, where there's potentially the most direct data. I think how you really make the decision is, if we're trying to potentially achieve significant shrinkage, then potentially certainly I would consider lenvatinib, just because it tends to be more potent and has a higher ORR. But if a patient had those exclusions that were part of the REFLECT trial previously, in terms of main portal vein invasion, then oftentimes I will choose cabozantinib in that setting, just because of the fact that the CELESTIAL trial had a broader eligibility allowing for those patients with main portal vein invasion.