Supplementary Material for: SAFETY AND EFFICACY OF ATEZOLIZUMAB/ BEVACIZUMAB IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND IMPAIRED LIVER FUNCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

BACKGROUND: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. OBJECTIVES: In this study we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analysing them by meta-analysis. METHOD: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. RESULTS: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (P=0.0001), with an Odds Ratio (OR) of 0.43 [confidence interval (CI) 0.21–0.90; P=0.02). Progression Free Survival (PFS) at both 6-month (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 Child-Pugh class B patients. A trend towards higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; P=0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; P=0.02). Median overall survival (OS) was 16.8±2.0 and 6.8±3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, P<0.0001). Lastly, OS was longer in patients with ALBI grade 1-2 than in those with grade 3 (8.3±11.4 versus 3.3±5.0 months, P=0.0008). CONCLUSIONS: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.