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

Purpose

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

Abbreviations

AE, Adverse events; BCLC, Barcelona Clinic Liver Cancer; CI, Confidence interval; CR, Complete response; DCR, Disease control rate; ICI, Immune checkpoint inhibitors; ORR, Objective response rate; OS, Overall survival; PD, Progressive disease; PFS, Progression-free survival; PR, Partial response; SD, Stable disease; TKI, Tyrosine kinase inhibitor; TRAE, Treatment-related adverse events; TTR, Time to response.

Data Sharing Statement

The data that support the findings of this study are available via a data access agreement. Please contact the corresponding author for this request.

Ethics Approval and Informed Consent

This study was approved by the Medical Ethics Committee of our hospital and registered in the Chinese Clinical Trial Registry (ChiCTR2100054041). All subjects voluntarily enrolled and signed written informed consent.

Acknowledgments

Thank all the staff authors for their contributions to this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

There is no funding to report.