Background & aims: At the pre-specified interim analysis (IA; median follow-up, 17.4 months), IMbrave050 met its primary endpoint of improved independent review facility (IRF)-assessed recurrence-free survival (RFS) in patients with high-risk hepatocellular carcinoma (HCC). The RFS hazard ratio (HR) for atezolizumab plus bevacizumab vs. active surveillance was 0.72 (adjusted 95% CI 0.53-0.98; p = 0.012), and overall survival (OS) data were immature. Here, we report an updated post hoc analysis of RFS and the second IA of OS, along with additional data.
Methods: IMbrave050 enrolled patients with HCC who had high recurrence risk following curative-intent resection or ablation. Patients were randomized 1:1 to receive atezolizumab 1,200 mg plus bevacizumab 15 mg/kg intravenously every 3 weeks (17 cycles) or active surveillance for 1 year; patients were eligible to cross over to atezolizumab plus bevacizumab following IRF-assessed recurrence. Stratification factors included geographic region and a composite factor comprising the number of high-risk features, curative procedure, and use of optional adjuvant transarterial chemoembolization (one cycle) post-resection. Secondary endpoints included OS and safety.
Results: In the updated analysis, RFS HR was 0.90 (95% CI 0.72-1.12). At the second IA, OS data remained immature (HR 1.26; 95% CI 0.85-1.87). RFS and OS results were consistent across clinically relevant subgroups. Updated safety data were consistent with the primary analysis.
Conclusions: In this updated analysis, the initial RFS benefit seen with atezolizumab plus bevacizumab vs. active surveillance was not sustained and OS data remained immature. The safety profile of atezolizumab plus bevacizumab remained manageable and consistent with that of each agent and the underlying disease. Overall, the benefit-risk profile does not support atezolizumab plus bevacizumab as adjuvant therapy.
Impact and implications: Based on results from the IMbrave150 trial, atezolizumab in combination with bevacizumab is the standard-of-care first-line treatment for unresectable hepatocellular carcinoma (HCC), prompting interest in investigating the combination in earlier treatment settings. IMbrave050 was the first immunotherapy study to report data in the adjuvant setting for HCC, where an early recurrence-free survival benefit was observed at the pre-specified interim analysis but not maintained with longer follow-up; overall survival data remained immature. The updated results of IMbrave050 do not support the use of atezolizumab plus bevacizumab in the adjuvant setting. However, subgroup analyses suggest a potential benefit in select patients, warranting further prospective evaluation. Effective perioperative or adjuvant treatment remains a major unmet need for patients with HCC given the high rate of early post-operative relapse.
Clinical trial number: NCT04102098.
Keywords: IMbrave050; adjuvant therapy; atezolizumab; bevacizumab; hepatocellular carcinoma.
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