Supplementary Material for: Transarterial Chemoembolization plus Sorafenib versus Sorafenib Alone in Advanced Hepatocellular Carcinoma (SELECT): a Multicenter, Phase 3, Randomized, Controlled Trial

Introduction: Patients with advanced hepatocellular carcinoma (HCC) face an extremely poor prognosis. Sorafenib, a multikinase inhibitor, remains an essential treatment for advanced HCC in certain clinical settings where immunotherapy is either contraindicated or unavailable. However, the survival benefit of transarterial chemoembolization (TACE) plus sorafenib remains under investigation.
Methods: The SELECT trial was a multicenter, randomized, controlled study conducted across twelve centers in China. From September 7, 2013, to December 4, 2019, 199 patients with advanced-stage HCC were randomly assigned in a 1:1 ratio to receive either TACE plus sorafenib or sorafenib monotherapy.
Results: The median age of the study population was 55 years (IQR 46-63), with hepatic virus infection being the predominant cause of HCC. In the intention-to-treat (ITT) population, the overall survival (OS) analysis did not show a statistically significant difference between the combination and sorafenib monotherapy groups (14.9 months [95%CI 10.5-19.3] vs. 11.9 months [95%CI 9.0-14.8], HR 0.862, P=0.312). However, the combination therapy group demonstrated significantly improved time to progression (TTP) (10.0 months [95%CI 6.4-13.6] vs. 5.9 months [95%CI 3.1-8.7]; P=0.016) and post-hoc progression-free survival (PFS) (8.5 months [95%CI 6.7-10.3] vs. 5.6 months [95%CI 4.1-7.1]; P=0.034). In predefined per-protocol analysis, the combination therapy group showed a significantly longer median OS compared to the monotherapy group (14.6 months [11.3-17.9] vs. 7.4 months [95%CI 4.3-10.5], HR 0.539, P=0.001).
Conclusion: Although the combination of TACE and sorafenib did not demonstrate a significant improvement in OS in the ITT analysis, it met the secondary endpoints, including TTP and post-hoc PFS. These findings provide valuable insights for the design of future trials and highlight the importance of integrating locoregional interventions with systemic therapies in the management of advanced-stage HCC.

引言：晚期肝细胞癌（hepatocellular carcinoma, HCC）患者预后极差。索拉非尼（sorafenib）作为一种多激酶抑制剂（multikinase inhibitor），在免疫治疗禁忌或无法开展的特定临床场景中，仍是晚期HCC的核心治疗手段。然而，经动脉化疗栓塞术（transarterial chemoembolization, TACE）联合索拉非尼的生存获益仍有待进一步研究。
方法：本研究依托SELECT试验开展，该试验为一项多中心随机对照研究，在中国12家中心同步实施。2013年9月7日至2019年12月4日期间，共纳入199例晚期HCC患者，以1:1的比例随机分配至TACE联合索拉非尼组与索拉非尼单药治疗组。
结果：研究人群的中位年龄为55岁，四分位距（interquartile range, IQR）为46~63岁，肝病毒感染是HCC的主要致病因素。在意向治疗（intention-to-treat, ITT）人群中，联合治疗组与索拉非尼单药组的总生存期（overall survival, OS）未呈现统计学显著性差异（14.9个月[95%置信区间10.5~19.3] vs 11.9个月[95%置信区间9.0~14.8]，风险比0.862，P=0.312）。但联合治疗组的疾病进展时间（time to progression, TTP）（10.0个月[95%置信区间6.4~13.6] vs 5.9个月[95%置信区间3.1~8.7]；P=0.016）及事后无进展生存期（post-hoc progression-free survival, PFS）（8.5个月[95%置信区间6.7~10.3] vs 5.6个月[95%置信区间4.1~7.1]；P=0.034）均显著优于单药组。在预设的符合方案分析（per-protocol analysis）中，联合治疗组的中位OS显著长于单药组（14.6个月[11.3~17.9] vs 7.4个月[95%置信区间4.3~10.5]，风险比0.539，P=0.001）。
结论：尽管在ITT分析中，TACE联合索拉非尼未使OS获得显著改善，但该联合方案达成了包括TTP及事后PFS在内的次要研究终点。本研究结果为未来临床试验的设计提供了重要参考，同时凸显了将局部区域治疗与全身治疗相结合在晚期HCC管理中的重要价值。