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.