Sorafenib Combined with Tislelizumab and Transarterial Chemoembolization for Advanced-Stage Hepatocellular Carcinoma: A Phase II Study

Licong Liang,1,2,* Jingwen Zhou,1,2,* Jingjun Huang,1,2,* Yongjian Guo,1,2 Zhimei Zhou,2,3 Ye Chen,1,2 Liteng Lin,1,2 Xiaoyang Hong,1,4 Wenbo Shi,1,5 Zhaoyi Lin,1,2 Juan Liu,1,2 Kangshun Zhu,1,2 Wensou Huang,1,2 Mingyue Cai1,2 1Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2GuangDong Engineering Technology Research Center of Interventional Oncology and Precision Drug Delivery, Guangzhou, People’s Republic of China; 3Department of Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Radiology, Yuebei People’s Hospital, Shaoguan, People’s Republic of China; 5Shanghai Clinical Research Ward (SCRW), Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingyue Cai, Email [email protected] Wensou Huang, Email [email protected]: To evaluate the efficacy and safety of sorafenib combined with tislelizumab (a programmed death-1 inhibitor) and transarterial chemoembolization (TACE) in patients with advanced-stage hepatocellular carcinoma (HCC).Patients and Methods: This was a single-center, single-arm phase II trial. Patients with HCC at Barcelona Clinic Liver Cancer stage C were recruited. Treatment with sorafenib (400 mg orally twice daily) and tislelizumab (200 mg intravenously every 3 weeks) was initiated 3– 7 days after the first TACE procedure. Repeated TACE was performed on-demand. The primary endpoint of this study was overall survival (OS).Results: Thirty patients were enrolled. The median OS for the patients was 18.3 (95% CI = 14.6– 22.0) months, with 12-, 18-, and 24-month OS rates of 90.0%, 54.0%, and 28.3%, respectively. The objective response rate was 53.3% per modified Response Evaluation Criteria in Solid Tumors (mRECIST) and 20.0% per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median progression-free survival was 6.8 (95% CI = 4.5– 9.0) months per mRECIST/RECIST 1.1. The median duration of response was 7.1 (95% CI = 6.1– 8.1) months per mRECIST (n = 16) and 4.4 (95% CI = 0.9– 7.9) months per RECIST 1.1 (n = 6). Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%), and grade 3 TRAEs were observed in 11 patients (36.7%). There were no grade 4/5 TRAEs.Conclusion: Sorafenib combined with tislelizumab and TACE showed promising antitumor activities with a manageable safety profile in patients with advanced-stage HCC. These preliminary findings warrant further evaluation in Phase III randomized trials.Keywords: hepatocellular carcinoma, sorafenib, tislelizumab, transarterial chemoembolization, combination therapy