Efficacy and Safety of Transarterial Chemoembolization Plus Donafenib with or without Immune Checkpoint Inhibitors as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Abstract

Purpose

To compare the efficacy and safety of transarterial chemoembolization (TACE) plus donafenib with immune checkpoint inhibitors (ICIs) (T+D+I) versus TACE plus donafenib (T+D) as the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC).

Methods

This retrospective study included patients with unresectable HCC who received T+D+I or T+D between June 2021 and February 2023. The tumor response was analyzed according to the modified Response Evaluation Criteria in Solid Tumors. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) in the two groups were compared before and after propensity score matching (PSM). Cox’s proportional-hazards regression model was used to analyze factors affecting PFS and OS.

Results

This study included 69 patients: 41 patients in the T+D group and 28 patients in the T+D+I group. After PSM, 26 patients in each group were analyzed. Patients in the T+D+I group had a higher DCR (96.2% vs 73.1%, P = 0.021), longer median PFS (13.1 vs 7.2 months, P = 0.017), and longer median OS (23.1 vs 14.7 months, P = 0.021) than those in the T+D group. The ORR in the two groups was similar (53.8% vs 50.0%, P = 0.781). Multivariate analyses revealed that T+D+I treatment and total bilirubin levels of <20 μmol/L were independent prognostic factors for long PFS. T+D+I treatment, Child–Pugh class A, and single-lobe tumor distribution were independent prognostic factors for long OS. The incidence of TRAEs in the two groups was similar (P > 0.05).

Conclusion

In comparison with TACE plus donafenib, TACE plus donafenib with ICIs could significantly improve DCR, PFS, and OS as a potential first-line treatment for unresectable HCC with an acceptable safety profile.

Keywords:

• unresectable hepatocellular carcinoma
• transarterial chemoembolization
• donafenib
• immune checkpoint inhibitor
• combined therapy

Disclosure

Guohui Xu and Xuegang Yang contributed equally to this work and share last authorship. The authors declare that there is no conflict of interest.

Additional information

Funding

This study has received funding by Natural Science Foundation of Sichuan (No. 2022NSFSC0837), Natural Science Foundation for Youtus of Sichuan (No. 2023NSFSC1635), Science and Technology Project of Chengdu (No. 2022-YF05-01811-SN), Beijing Medical Award Foundation (Grant No. YXJL-2020-0972-0424), Beijing Xisike Clinical Oncology Research Foundation (Grant No. Y-HR2020MS-0484).