Q&A: Longest survival among HCC patients seen with ‘breakthrough’ drug combination

In an exclusive interview with Healio Gastroenterology, Richard Finn, MD, discussed the results from a recent study of patients with hepatocellular carcinoma treated with combination therapy comprising atezolizumab, an immunotherapy drug and monoclonal antibody, and bevacizumab, another monoclonal antibody against the vascular endothelial growth factor (VEGF).

The data presented at the Digital Liver Cancer Summit 2021 was an update to a trial initially published with 8.6-months follow-up published in The New England Journal of Medicine. Finn, professor in the department of medicine, division of hematology/oncology, director of signal transduction and therapeutics program at the Jonsson Comprehensive Cancer at the Geffen School of Medicine at University of California, Los Angeles, and colleagues included 501 patients with HCC in the open label, randomized controlled trial. Patients received either the combination therapy of atezolizumab (Tecentriq, Genentech) plus bevacizumab (Avastin, Genentech) or sorafenib (Nexavar; Bayer) alone.

At 12 months, survival was 67.2% in the atezolizumab plus bevacizumab group, compared with 54.6% sorafenib-alone group. At 18 months, survival was 52% with atezolizumab plus bevacizumab vs. 40% with sorafenib.

Healio: What was the purpose and design of the study?

Finn: We presented updated results from the IMbrave150 study. This was a phase 3, randomized study of atezolizumab and bevacizumab vs. sorafenib in patients with advanced liver cancer. This was a frontline study for an area of unmet need because no drug or regimen had ever been shown to be superior to sorafenib since its approval in 2008 in terms of overall survival.

We randomized patients in an open-label fashion 2:1 and published the initial results The New England Journal of Medicine last May. Those data supported the global approval of the regimen starting in the U.S. in June, and since that time it’s been rolling out globally. It showed a significant improvement in overall survival but at the first analysis, the data were not mature for OS with atezolizumab and bevacozumab, meaning we did not have the true median in the treatment arm. The hazard ratio was 0.58 and the study was stopped at the first interim analysis, but we did not have longer-term follow up at that time. The study had a very nice response rate at the first analysis of 27%, and at EASL we had an initial 12 months of follow-up so now the median follow-up was over 15 and a half months.

We now present results with these updated OS data knowing that the true median for first line liver cancer with this combination therapy is over 19 months. It was 19.2 months vs. 13.4 months with sorafenib. That is a big improvement considering we’ve been trying to do this for a long time. The other updated data are that we confirmed the progression-free survival benefit. It’s maintained its separation and responses have increased. We actually have a response rate of 30% now, which includes 8% complete responses. And we have the true median duration of response, which is 18.1 months. This is coupled with the fact that there’s no new safety data concerns that showed up. It’s very consistent with the primary analysis. We also presented for the first-time detailed subgroup analysis for survival, PFS and response and we see that this benefit is very much consistent across etiologies and regions and other prognostic factors in liver cancer.

Healio: What are the key takeaways?

Finn: This doublet is probably now the standard of care for patients who have advanced liver cancer. These are patients who have disease outside the liver or disease in the liver that’s invading the vasculature or patients who have had local regional treatments that are no longer benefitting them. Systemic treatments such as this are very active and there’s no longer a need to continue to use local regional treatments beyond progression, which has been a tendency because systemic treatments haven’t offered these large gains.

Healio: What was the conclusion of the study and next step in research?

Finn: The primary analysis was what was in The New England Journal of Medicine; the stats and everything were designed for that analysis, but we will continue to follow patients for longer follow-up. There’s biomarker work being done as well, so the study’s still ongoing in that regard. It’s obviously closed to approval for some time, but there’s going to be longer-term follow-up as well.

This really sets the benchmark for front line liver cancer and that there are several other phase 3 studies we’re waiting for and those results will all be benchmarked to the results of this study.