The FDA approved atezolizumab in combination with bevacizumab for the treatment of patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.
The FDA has approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy, according to Genentech, the agent’s developer.
Simultaneous applications for use of the combination were submitted to regulators in the US, Australia, Canada, and Singapore under Project Orbis. Additionally, the FDA reviewed and approved the application under its real time oncology review pilot program.
“We're excited that today’s approval of (atezolizumab) in combination with (bevacizumab) for unresectable or metastatic hepatocellular carcinoma brings a cancer immunotherapy option to people with this aggressive form of liver cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a press release.
The approval was based on results from the global, multicenter, open-label, phase III IMbrave150 study, which evaluated 501 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Participants were randomized in a 2:1 ratio to receive either the combination of atezolizumab and bevacizumab or sorafenib (Nexavar).
Patients were intravenously (IV) administered 1200 mg of atezolizumab on day 1 of each 21-day cycle, and 15 mg/kg of bevacizumab by IV on day 1 of each 21-day cycle. Sorafenib was administered orally at a dose of 400 mg twice per day, on days 1-21 of each 21-day cycle. Participants received the combination or the control arm treatment until disease progression or unacceptable toxicity.
The 2 primary end points were overall survival (OS) and independent review facility (IRF)-assessed PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Key secondary study end points were IRF-assessed overall response rate (ORR) per RECIST and mRECIST.
Atezolizumab in combination with bevacizumab demonstrated an OS rate of 42% (HR, 0.58; 95% CI, 0.42-0.79; P = 0.0006) and a progression-free survival (PFS) rate of 41% (HR, 0.59; 95% CI, 0.47-0.76; P < 0.0001), compared with sorafenib. IMbrave150 is the first phase III immunotherapy study to show an improvement in OS and PFS in individuals with unresectable or metastatic HCC compared with sorafenib.
Grade 3 to 4 serious adverse events (AEs) occurred in 38% of those treated with atezolizumab and bevacizumab. The most frequent serious AEs (≥2%) were bleeding in the gastrointestinal tract, infections, and fever.
“The results of the IMbrave150 study are really transformative for patients with advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,” Richard S. Finn, MD, professor of Medicine at the David Geffen School of Medicine at UCLA and director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center, said in the release. “For the first-time we have a regimen that markedly improves survival over sorafenib, the standard of care for first-line hepatocellular carcinoma since 2007, and offers patients the opportunity for improved disease control with a favorable tolerability profile.”
Genentech indicated that there are multiple ongoing and planned phase III studies of atezolizumab across several types of lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. These studies include evaluating atezolizumab both alone and in combination with other medicines.
FDA Approves Genentech’s Tecentriq in Combination with Avastin for People With the Most Common Form of Liver Cancer [news release]. South San Francisco, CA. Published May 29, 2020. gene.com/media/press-releases/14856/2020-05-29/fda-approves-genentechs-tecentriq-in-com. Accessed May 29, 2020.