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 analyzing them by meta-analysis. Methods 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 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a 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 grades 1-2 than in those with grade 3 (8.3 ± 11.4 vs. 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.

中文翻译：

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Atezolizumab/贝伐单抗在肝细胞癌和肝功能受损患者中的安全性和有效性：系统评价和荟萃分析。


背景 阿特朱单抗/贝伐单抗在 Child-Pugh B 级肝细胞癌 (HCC) 患者中的安全性和结果尚未完全确定。目的 在本研究中，我们旨在通过回顾现有数据并通过荟萃分析来分析 atezolizumab/贝伐单抗在 Child-Pugh B 患者中的安全性和有效性。方法 我们比较了 atezolizumab/becavizumab 治疗不可切除的 HCC 和不同程度肝功能障碍患者的安全性和有效性。本荟萃分析共纳入 8 项回顾性、非随机队列研究，涉及总共 1,071 名 Child-Pugh A 型患者和 225 名 Child-Pugh B 型患者。白蛋白-胆红素 (ALBI) 等级也可用于评估肝功能（如果有）。结果 Child-Pugh A 级患者中 11.8% 和 B 级患者中 26.8% 发生≥3 级不良事件 (p = 0.0001)，比值比 (OR) 为 0.43（置信区间 [CI] 0.21-0.90；p = 0.02）。 Child-Pugh 组的 6 个月（4.90 ± 2.08 对比 4.75 ± 2.08 个月；p = 0.0004）和 12 个月（8.83 ± 2.32 对比 7.26 ± 2.33 个月；p = 0.002）的无进展生存期 (PFS) 较低B 类患者。与 Child-Pugh B 级患者 (25/138, 18.1%; p = 0.070) 相比，Child-Pugh A 级患者 (219/856, 25.6%) 观察到客观缓解率 (ORR) 较高的趋势，而 Child-Pugh A 级患者获得 ORR 的概率明显更高（OR 1.79，CI 1.12-2.86；p = 0.02）。 Child-Pugh A 型和 B 型患者的中位总生存期 (OS) 分别为 16.8 ± 2.0 和 6.8 ± 3.2 个月（平均差异 9.06 个月，CI 7.01-11.1，p < 0.0001）。最后，ALBI 1-2 级患者的 OS 比 3 级患者更长（8.3 ± 11.4 个月与 3.3 ± 5.0 个月，p = 0.0008）。 结论 在 Child-Pugh B 级患者中，阿特珠单抗/贝伐单抗的肿瘤学疗效中等，并且这些患者中观察到的较短的 PFS 和 OS 与经历治疗相关不良事件的可能性更大相关，这表明治疗需要高度谨慎和个体化，可能需要考虑支持 ALBI 等级。