On May 29, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) for the treatment of people with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.
The review of this application was conducted under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners. Simultaneous applications were submitted to regulators in the United States, Australia, Canada and Singapore, under Project Orbis. Additionally, the FDA rapidly reviewed and approved the application under its Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.
IMbrave150
The approval was based on results from the phase III IMbrave150 study, a global, multicenter, open-label study of 501 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomly assigned 2:1 to receive atezolizumab/bevacizumab or sorafenib.
Atezolizumab was administered intravenously (IV) at 1,200 mg on day 1 of each 21-day cycle, and IV bevacizumab was administered at 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered orally at 400 mg twice per day on days 1 through 21 of each 21-day cycle. Patients received the combination or the control arm treatment until disease progression or unacceptable toxicity.
The two primary endpoints were overall survival and independent review facility–assessed progression-free survival per Response Evaluation Criteria in Solid Tumors, version 1.1). Additional study endpoints were independent review facility–assessed overall response rate (ORR).
The trial demonstrated that treatment with atezolizumab plus bevacizumab improved overall survival by 42% (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.42–0.79, P = .0006) and improved progression-free survival by 41% (HR = 0.59, 95% CI = 0.47–0.76, P < .0001) compared with sorafenib. IMbrave150 is the first phase III cancer immunotherapy study to show an improvement in overall and progression-free survival in people with unresectable or metastatic HCC compared with sorafenib.
Serious adverse reactions (grade 3–4) occurred in 38% of people in the combination arm. The most frequent serious adverse reactions (≥ 2%) were bleeding in the gastrointestinal tract, infections, and fever.
These results were recently published in the The New England Journal of Medicine.
