Efficacy and Safety Analysis of Transarterial Chemoembolization Plus Donafenib With or Without Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Prospective, Single-Arm, Single-Center, Phase II Clinical Study

Abstract

Jinpeng Li,1,2 Yan Li,3 Jinlong Song,2 Lujun Zhao1 1Department of Radiation Oncology,Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People’s Republic of China; 2Department of Interventional Therapy I, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 3Department of Radiology, Shanghai People’s Hospital, Jinan, 250000, People’s Republic of ChinaCorrespondence: Lujun Zhao, Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People’s Republic of China, Tel [phone], Email [email protected] Jinlong Song, Department of Interventional Therapy I, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel [phone], Email [email protected]: To observe and assess the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) to treat unresectable hepatocellular carcinoma (HCC).Patients and Methods: This prospective, single-arm, single-center, phase II clinical study enrolled 36 patients with initial unresectable HCC who had not undergone any systemic treatment. The patients received donafenib plus TACE (n = 26) or donafenib plus TACE plus programmed death receptor 1 inhibitors (n = 10). The primary endpoint was short-term efficacy, with secondary endpoints including progression-free survival (PFS), time to response (TTR), disease control rate (DCR), and adverse events. The tumor feeding artery diameter was also measured.Results: Efficacy evaluation of all 36 patients revealed 6 cases of complete response, 19 of partial response, 8 of stable disease, and 3 of progressive disease. Six (16.7%) patients successfully underwent conversion surgery, all achieving R0 resection, and 2 (5.6%) achieved a complete pathological response. The objective response rate (ORR) was 69.4% and the DCR was 91.7%. The median PFS was 10.7 months, the median overall survival was not reached, and the median TTR was 1.4 months. The median survival rates at 6, 12, and 18 months were 85.0%, 77.6%, and 71.3%, respectively. The median PFS rates at 6, 12, and 18 months were 65.3%, 45.6%, and 34.2%, respectively. Treatment-related adverse events (TRAEs) occurred in all 25 subjects, including 4 (11.3%) grade 3 TRAEs. No grade 4 or 5 TRAEs occurred. The tumor feeding artery diameter was significantly decreased following treatment (P = 0.036). Multivariable analysis revealed the sum of baseline target lesion diameters, best tumor response, and combined immunotherapy as independent predictors of PFS.Conclusion: TACE plus donafenib reduced the tumor feeding artery diameter in patients with unresectable HCC. The safety profile was good, and a high ORR was achieved.Keywords: hepatocellular carcinoma, donafenib, transarterial chemoembolization, immune checkpoint inhibitors, safety, efficacy

Keywords

• hepatocellular carcinoma
• donafenib
• transarterial chemoembolization
• immune checkpoint inhibitors
• safety
• efficacy