Phase II Study of Atezolizumab and Bevacizumab Combination Therapy for Patients with Advanced Hepatocellular Carcinoma Previously Treated with Lenvatinib.

Background/Objectives: Atezolizumab and bevacizumab combination therapy has been established as a standard of care for first-line treatment; however, its efficacy and safety have not been fully evaluated for patients previously treated with systemic therapy. Methods: In this phase II trial, patients with advanced hepatocellular carcinoma previously treated with lenvatinib were enrolled to receive a dose of 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, disease control rate, subsequent therapy, and frequency of adverse events. The threshold and expected progression-free survival were 3 and 6.8 months, respectively. Considering a one-sided significance level of 0.05 and a statistical power of 80%, the minimum required sample size was 26 patients. Results: The median progression-free survival from the start of treatment was 9.70 [90% confidence interval, 5.10-14.24] months, and the lower limit of the 90% CI was above the predefined threshold. The objective response and disease control rates were 34.6% and 73.1%, respectively. Sixteen patients (61.5%) received subsequent therapies, and the median overall survival was 17.23 [90% confidence interval, 13.18-27.85] months. Severe adverse events, adverse events leading to treatment delays, and adverse events leading to treatment discontinuation occurred in eight (30.8%), fourteen (53.8%), and five (19.2%) patients, respectively, and no treatment-related deaths occurred. Conclusions: Atezolizumab and bevacizumab combination therapy is effective and can safely be administered to patients with advanced HCC previously treated with lenvatinib.