Drug Combo Yields Longest-Ever Survival In Advanced Liver Cancer

The combination of atezolizumab and bevacizumab has yielded the longest overall survival ever seen in a phase 3 study of patients with previously untreated, nonresectable, advanced hepatocellular carcinoma (HCC), according to updated results from the IMbrave150 study.

"The updated data from the IMbrave150 study is very exciting," Dr. Richard Finn, with the Jonsson Comprehensive Cancer Center at University of California Los Angeles (UCLA), told Reuters Health by email.

"We now have a new standard for front-line HCC." The survival is "longer than anything we have seen at 19.2 months. This is accompanied by very robust response data; a response rate of 30% including 8% complete responses," said Dr. Finn.

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He presented the updated data at the European Association for the Study of the Liver (EASL) Virtual Liver Cancer Summit 2021.

Atezolizumab is an immune-checkpoint inhibitor and bevacizumab is an anti-VEGF targeted monoclonal antibody.

The IMbrave150 trial enrolled 501 patients with nonresectable, treatment-naive HCC; 336 were randomly allocated to atezolizumab (1,200 mg IV every three weeks) plus bevacizumab (15 mg/kg IV every three weeks) and 165 to sorafenib (400 mg twice daily).

Results of the primary analysis, published in the New England Journal of Medicine last spring, were based on median follow-up of 8.6 months and showed a survival advantage with the atezolizumab-bevacizumab combination.

Now, after a median follow-up of 15.6 months, median overall survival was 19.2 months in patients treated with the combination versus 13.4 months in those treated with sorafenib (hazard ratio, 0.66; 95% confidence interval, 0.52 to 0.85).

Overall survival at 18 months was 52% with combination therapy versus 40% with sorafenib, Dr. Finn reported at the EASL conference.

The survival benefit with atezolizumab plus bevacizumab versus sorafenib was "generally consistent across subgroups and with the primary analysis. Safety was consistent with the primary analysis, with no new safety signals," according to the conference abstract.

"IMbrave150 showed consistent clinically meaningful treatment benefit and safety with an additional 12 months of follow-up," Dr. Finn said in the news release.

In a phone interview with Reuters Health, Dr. Augusto Villanueva, Assistant Professor of Medicine, Liver Diseases and Hematology/Medical Oncology at the Tisch Cancer Institute at Mount Sinai in New York, said, "The results in terms of median survival are remarkable for this deadly disease. For the first time in more than 10 years we have something that is better than what we had in the past as first-line."

Dr. Villanueva, who wasn't involved in the study, said it's also noteworthy that 30% of patients had an objective response to the combination and the median duration of response was one year. "That's remarkable for liver cancer, and the quality of life with the new combination was better than with sorafenib," he said.

In email to Reuters Health, Dr. Finn said, "It is important that clinicians realize that the systemic treatment for HCC has evolved, no longer is it a 'one drug' disease but we have very active regimens that are markedly improving survival and maintains a patient's quality of life. With that in mind, patients need to start systemic therapy at an appropriate time in their disease course and not wait until they decompensate from their liver disease to start these therapies."

"Patients with intermediate stage HCC that are not responding to, or progressing after transarterial chemoembolization (TACE) or yttrium-90 (Y90) with tumor growth or developing vascular invasion should be transitioned to systemic therapy, not just continued on these procedure based approaches," he added.

Looking ahead, Dr. Finn said, "we will need to identify paradigms for sequencing all the drugs we now have available for HCC and its not too early to think about how do we do better in the front-line setting; what do we add on to this backbone?"

The IMbrave150 trial was funded by Genentech/Roche.

—Megan Brooks

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