The combination of atezolizumab and bevacizumab prolonged survival compared with standard-of-care sorafenib for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy, according to topline data from the phase 3 IMbrave150 study.
This is the first phase 3 study to show improvements in OS and PFS with immunotherapy for the most common form of liver cancer.
Atezolizumab (Tecentriq, Genentech) is a monoclonal antibody designed to bind with PD-L1. Bevacizumab (Avastin, Genentech) is a VEGF inhibitor.
The FDA last year granted breakthrough therapy designation to the combination as treatment for HCC based on results from an ongoing phase 1b trial.
The multicenter, open-label IMbrave150 study included 501 patients with unresectable HCC who had not received prior systemic therapy.
Researchers randomly assigned two-thirds of patients to atezolizumab dosed at 1,200 mg IV plus bevacizumab dosed at 15 mg/kg IV on day 1 of each 21-day cycle. One-third of patients received standard treatment with the multikinase inhibitor sorafenib (Nexavar, Bayer), dosed at 400 mg orally twice daily.
Treatment continued until unacceptable toxicity or investigator-determined loss of clinical benefit.
The study met its co-primary endpoints of improved OS and PFS with the atezolizumab-bevacizumab combination. Secondary endpoints included overall response rate, time to progression, duration of response, patient-reported outcomes, safety and pharmacokinetics.
The safety profile of the combination appeared consistent with the known safety profiles of each individual agent. Researchers observed no new safety signals.
Complete data from IMbrave150 will be submitted for presentation at a future medical meeting. They also will be submitted to the FDA and other regulatory health authorities, according to a Genentech-issued press release.
“We are very pleased with the results of our study testing the combination of Tecentriq and Avastin, which marks the first treatment in more than a decade to improve overall survival in people with unresectable hepatocellular carcinoma who have not received prior systemic therapy,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release. “HCC is a major cause of death globally and particularly in Asia, making this study an important step in our mission of addressing unmet medical needs for patients around the world. ... Our hope is to bring a new treatment to people with this aggressive disease who currently have limited options.”