Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience

SIMPLE SUMMARY: Hepatocellular cancer is the most common type of primary liver cancer. It is the third leading cause of cancer-related deaths worldwide and its incidence is increasing: >1 million new cases per year expected by 2025. Despite advances in treatment in recent years, diagnosis is associated with poor overall survival. Treatment of hepatocellular cancer depends on the patient’s general health and fitness, how well the liver is working, the number and size of tumors in the liver, and whether or not the tumor has spread to other neighboring or distant parts of the body. The combination of atezolizumab plus bevacizumab, two intravenously administered antibodies, is the preferred first-line treatment for patients with advanced hepatocellular cancer that has spread from the liver to other neighboring or distant parts of the body. This study investigated how long patients whose hepatocellular cancer continues to grow (progress) despite one or more prior tumor therapies live when they receive atezolizumab plus bevacizumab. These patients, treated with atezolizumab plus bevacizumab at various hospitals in Germany and Austria, lived about 16 months, which is about 5–8 months longer than patients receiving approved drugs. The safety profile was consistent with previous reports. ABSTRACT: Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Methods: Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria. Patient characteristics, tumor response rates, progression-free survival (PFS), overall survival (OS), and adverse events (AE) were analyzed. Results: A total of 50 patients were identified; 41 (82%) were male. The median age at initiation of treatment with atezolizumab plus bevacizumab was 65 years, 41 (82%) patients had cirrhosis, 30 (73%) Child A, 9 (22%) B, and 2 (5%) C. A total of 34 patients (68%) received atezolizumab plus bevacizumab in the second-line setting and 16 (32%) in later lines. The best radiologic tumor responses were complete remission (2%), partial remission (30%), stable disease (36%), and progressive disease (18%), resulting in an objective response rate of 32% and a disease control rate of 68%. Median OS was 16.0 months (95% confidence interval 5.6–26.4 months), and median PFS was 7.1 months (95% confidence interval 4.4–9.8 months). AE grades 3–4 were observed in seven (14%) and resulted in death in three patients (6%). There were five (10%) bleeding events with a grade ≥ 3, including one (2%) with a fatal outcome. Conclusions: Atezolizumab plus bevacizumab is effective in patients with aHCC who did not have access to this option as first-line therapy. The safety profile was consistent with previous reports.