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

Yan Zhao; Wei Bai; Rong Ding; Nan You; Lin Zheng; Lei Li; Jianbing Wu; Peng Zhang; Wukui Huang; Hui Zhang; Yongjin Zhang; Diwen Zhu; Haiping Li; Dongdong Xia; Jie Yuan; Xiaomei Li; Zhengyu Wang; Bohan Luo; Wengang Guo; Zhanxin Yin; Wei Mu; Ming Huang; Jing Li; Weixin Ren; Daiming Fan; Yong Lv; Guohong Han

doi:10.1159/000546530

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

Liver Cancer. 2025 May 22:1-14. doi: 10.1159/000546530. Online ahead of print.

Authors

Yan Zhao^{1

2}, Wei Bai^{1

2}, Rong Ding³, Nan You⁴, Lin Zheng⁵, Lei Li⁶, Jianbing Wu⁷, Peng Zhang⁸, Wukui Huang⁹, Hui Zhang¹⁰, Yongjin Zhang¹¹, Diwen Zhu¹², Haiping Li¹³, Dongdong Xia², Jie Yuan¹, Xiaomei Li¹, Zhengyu Wang¹, Bohan Luo¹, Wengang Guo¹, Zhanxin Yin¹, Wei Mu¹⁰, Ming Huang³, Jing Li⁴, Weixin Ren¹², Daiming Fan², Yong Lv², Guohong Han^{1

2}

Affiliations

¹ Department of Liver Diseases and Interventional Radiology, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.
² Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Disease, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
³ Department of Minimally Invasive Intervention, Yunnan Cancer Hospital, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
⁴ Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
⁵ Department of Interventional Radiology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Interventional Medicine, First Affiliated Hospital of Lanzhou University, Lanzhou, China.
⁷ Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
⁸ Department of Interventional Radiology, Affiliated Hospital of Qinghai University, Qinghai, China.
⁹ Department of Interventional Radiology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
¹⁰ Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
¹¹ Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People's Hospital, Changsha, China.
¹² Department of Interventional Radiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
¹³ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

Abstract

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.

Keywords: Barcelona clinic liver cancer; Hepatocellular carcinoma; Overall survival; Sorafenib; Transarterial chemoembolization.