Systematic review and meta-analysis of safety and efficacy of atezolizumab/ bevacizumab in Child-Pugh class B patients with hepatocellular carcinoma

Introduction The safety and efficacy of atezolizumab/bevacizumab in patients with hepatocellular carcinoma (HCC) and impaired liver function is not completely defined. Aims To address safety and efficacy of atezolizumab/bevacizumab in Child-Pugh class B patients reviewing the published data and analysing them by meta-analysis. Materials and Methods Safety and efficacy of atezolizumab/becavizumab in patients with HCC and Child-Pugh B cirrhosis were compared to the respective figures in Child-Pugh A patients. Overall, 8 retrospective, non-randomized, cohort studies were identified, including a total of 1,071 class A and 225 class B patients. Results Adverse events grade ≥3 were observed in 11.8% and 26.8% of class A and B patients, respectively (P=0.0001; Odds Ratio 0.43, confidence interval 0.21–0.90; P=0.02). Median overall survival was 16.8±2.0 and 6.8±3.2 months in class A and B patients, respectively (mean difference 9.06 months, 7.01–11.1, P<0.0001). Progression Free Survival at both 6- (4.90±2.08 vs 4.75±2.08 months; P=0.0004) and 12-month (8.83±2.32 vs 7.26±2.33 months; P=0.002) was lower in class B patients. A trend towards higher Objective Response Rate (ORR) (25.6% vs 18.1%, P=0.070) and a significantly greater probability of obtaining an ORR was observed in class A patients (Odds Ratio 1.79, 1.12–2.86, P=0.02). Disease Control Rate (DCR) was observed in 78.4% of class A and in 66.9% of class B patients (P=0.102), although class A had significantly higher probability of DCR than class B patients (Odds Ratio 1.73, 1.17–2.56; P=0.006). Conclusions Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter survival figures associated with a greater likelihood of experiencing treatment-related adverse events observed in these patients compared to patients with less impaired liver function suggest caution and individualization of treatment. Comparative studies with best supportive care may provide further evidence supporting treatment in these patients.