Supplementary Material for: Real-world study of systemic treatment after first-line atezolizumab plus bevacizumab for hepatocellular carcinoma in Asia-Pacific countries

Introduction: Atezolizumab plus bevacizumab is a commonly used first-line regimen for advanced hepatocellular carcinoma (HCC) treatment owing to its superior outcomes compared to sorafenib. However, optimal subsequent treatment options for patients with HCC who progressed on first-line atezolizumab plus bevacizumab remain unclear.
Methods: This multinational, multi-institutional, retrospective study included patients with HCC from 22 centers in five Asia-Pacific countries who were treated with first-line atezolizumab plus bevacizumab, which was discontinued for any reason. The endpoints included progression-free survival (PFS) and overall survival (OS) according to patient characteristics and second-line regimens.
Results: Between June 2016 and May 2023, 1141 patients were treated with first-line atezolizumab plus bevacizumab, of whom 629 (55.1%) received subsequent treatment. Sorafenib and lenvatinib were the most commonly administered second-line regimens (53.9% and 25.6%, respectively). Overall, the median PFS and OS were of 2.9 and 8.0 months, respectively. Lenvatinib had longer PFS (4.0 vs 2.3 months) and OS (8.0 vs 6.3 months) than sorafenib. Patients treated with tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) (n=50, 8.3%) showed PFS and OS of 5.4 and 12.6 months, respectively. Lower tumor burden and lenvatinib or TKI plus ICI use were associated with longer second-line PFS. Preserved liver function was associated with improved OS.
Conclusions: In patients with HCC who progressed on first-line atezolizumab plus bevacizumab, sorafenib and lenvatinib were the most commonly used second-line regimens in Asia-Pacific countries, with lenvatinib resulting in longer OS than sorafenib. The second-line TKI plus ICI combination exhibited promising efficacy, suggesting the potential role of continuing ICIs beyond disease progression.

引言：相较于索拉非尼（sorafenib），阿替利珠单抗（atezolizumab）联合贝伐珠单抗（bevacizumab）的疗效更优，因此是晚期肝细胞癌（hepatocellular carcinoma, HCC）一线治疗的常用方案。然而，对于一线接受阿替利珠单抗联合贝伐珠单抗治疗后出现疾病进展的HCC患者，其最佳后续治疗方案仍不明确。

方法：本项多国家、多中心回顾性研究纳入了亚太地区5个国家22家医疗中心的HCC患者，这些患者均接受过一线阿替利珠单抗联合贝伐珠单抗治疗，且因任意原因终止了该一线治疗方案。研究终点为基于患者基线特征与二线治疗方案的无进展生存期（progression-free survival, PFS）与总生存期（overall survival, OS）。

结果：2016年6月至2023年5月期间，共计1141例患者接受了一线阿替利珠单抗联合贝伐珠单抗治疗，其中629例（55.1%）接受了后续治疗。索拉非尼与仑伐替尼（lenvatinib）是最常用的二线治疗方案（占比分别为53.9%与25.6%）。整体而言，患者的中位PFS与中位OS分别为2.9个月与8.0个月。相较于索拉非尼，仑伐替尼治疗患者的PFS（4.0个月 vs 2.3个月）与OS（8.0个月 vs 6.3个月）均更长。接受酪氨酸激酶抑制剂（tyrosine kinase inhibitor, TKI）联合免疫检查点抑制剂（immune checkpoint inhibitor, ICI）治疗的患者（n=50，8.3%），其PFS与OS分别为5.4个月与12.6个月。较低的肿瘤负荷、使用仑伐替尼或TKI联合ICI方案与更长的二线PFS相关；肝功能储备良好则与更优的OS相关。

结论：对于一线接受阿替利珠单抗联合贝伐珠单抗治疗后出现疾病进展的HCC患者，索拉非尼与仑伐替尼是亚太地区最常用的二线治疗方案，且仑伐替尼的OS优于索拉非尼。二线TKI联合ICI方案展现出良好的疗效，提示在疾病进展后继续使用免疫检查点抑制剂或具有潜在临床价值。