As reported in The Lancet by Shukui Qin, MD, and colleagues, interim analysis of the phase III IMbrave050 trial has shown significantly better recurrence-free survival with adjuvant atezolizumab/bevacizumab vs active surveillance in patients who underwent curative-intent resection or ablation for high-risk hepatocellular carcinoma.
Shukui Qin, MD
Study Details
In the open-label trial, 668 patients from sites in 26 countries were randomly assigned between December 2019 and November 2021 to receive atezolizumab at 1,200 mg plus bevacizumab at 15 mg/kg every 3 weeks for 17 cycles (n = 334) or active surveillance (n = 334). A total of 83% of patients in the atezolizumab/bevacizumab group and 81% in the active surveillance group were Asian. The primary endpoint was recurrence-free survival on independent review facility assessment in the intention-to-treat population.
Key Findings
At the prespecified interim analysis, median duration of follow-up was 17.4 months (interquartile range [IQR] = 13.9–22.1 months). A total of 33% of patients in the combination group vs 40% of patients in the surveillance group had recurrence-free survival events. Median recurrence-free survival was not evaluable (95% confidence interval [CI] = 22.1 months to not evaluable) in the atezolizumab/bevacizumab group vs not evaluable (95% CI = 21.4 months to not evaluable) in the active surveillance group (hazard ratio = 0.72, 95% CI = 0.53–0.98, P = .012). The rate at 12 months was 78% vs 65%. A total of 67% and 66% of recurrences were intrahepatic.
The most common adverse events of any grade in the combination group were proteinuria (46%), hypertension (38%), and decreased platelet count (20%). Grade 3 or 4 adverse events occurred in 41% vs 13% of patients; those with a ≥ 2% higher frequency in the combination group were hypertension (18% vs 1%), proteinuria (9% vs 0%), and decreased platelet count (5% vs 1%). Adverse events led to discontinuation of both atezolizumab and bevacizumab in 9% of patients. Two deaths in the combination group were considered potentially related to treatment, due to varices hemorrhage and ischemic stroke.
The investigators concluded, “Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab vs active surveillance. To our knowledge, IMbrave050 is the first phase III study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.”
Pierce K.H. Chow, MD, of the National Cancer Centre Singapore, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit thelancet.com.
