The FDA has approved atezolizumab (Tecentriq®, Genentech, Inc.) in combination with bevacizumab (Avastin®, Genentech, Inc.) for patients with locally advanced unresectable or metastatic hepatocellular carcinoma (HCC) who have not previously received systemic therapy.
The approval was based on IMbrave150 (NCT03434379), a phase 3 trial that enrolled 501 patients with unresectable HCC. Patients were randomized in a 2:1 ratio to receive atezolizumab 1,200 mg administered intravenously followed by bevacizumab 15 mg/kg intravenously on the same day once every 3 weeks, or sorafenib taken orally twice daily. The study's primary end points were overall survival and progression-free survival, with secondary end points of overall response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified RECIST (mRECIST).
Compared with sorafenib, atezolizumab/bevacizumab significantly increased overall survival rate at 12 months (67.2% vs 54.6%) and median progression-free survival (6.8 vs 4.3 months). Patients receiving atezolizumab/bevacizumab experienced a higher overall response rate compared with sorafenib, according to both RECIST 1.1 (28% vs 12%) and mRECIST (33% vs 13%).
Grade 3/4 treatment-related adverse events occurred in 56.5% of patients receiving atezolizumab/bevacizumab, compared with 55.1% of patients receiving sorafenib. Grade 3/4 hypertension occurred in 15.2% of patients receiving atezolizumab/bevacizumab; other grade 3/4 adverse events were infrequent. Adverse events of any grade occurring in at least 20% of patients treated with atezolizumab/bevacizumab included hypertension, fatigue, and proteinuria.
"In patients with unresectable HCC, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib," conclude the study's investigators, led by first author Richard S. Finn, MD, Professor of Medicine at the David Geffen School of Medicine at the University of California Los Angeles, in their May publication in the New England Journal of Medicine.
The recommended dose of atezolizumab is 1,200 mg followed by bevacizumab 15 mg/kg on the same day once every three weeks. In the event that bevacizumab is discontinued, the recommended dose of atezolizumab alone is 840 mg every 2 weeks; 1,200 mg every three weeks; or 1,680 mg every four weeks.
For More Information
Clinicaltrials.gov (2020). A study of atezolizumab in combination with bevacizumab compared with sorafenib in patients with untreated locally advanced or metastatic hepatocellular carcinoma (IMbrave 150). NLM identifier:NCT03434379.
US Food and Drug Administration (2020). FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma
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