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TACE combined with regorafenib with or without anti-PD-1 therapy for advanced HCC after targeted therapy failure: a
Yan Li1, Hang Yuan1, Quan-Jun Yao1
1Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Background And Objectives:
Patients with hepatocellular carcinoma (HCC) progressing after targeted therapy face limited treatment options and poor prognosis. Although regorafenib is an established second-line therapy, its combination with locoregional and immunotherapeutic approaches remains insufficiently characterized in real-world settings. This multicenter study evaluated the efficacy and safety of combining transarterial chemoembolization (TACE) with regorafenib and anti-PD-1 therapy in advanced HCC (BCLC B/C) after targeted therapy failure, with a focus on optimizing treatment timing and dosing strategies.
Methods:
We conducted a retrospective, multicenter, propensity score-matched study involving 188 HCC patients from five tertiary medical centers between June 2022 and June 2024. Among them, 103 patients received triple therapy (TRP group: TACE combined with regorafenib and PD-1 inhibitors), while 85 received dual therapy (TR group: TACE combined with regorafenib). After propensity score matching (PSM), 64 patients were included in each group. Primary endpoints included progression-free survival (PFS) and overall survival (OS), evaluated per mRECIST v1.1 criteria, with secondary endpoints including objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Subgroup analyses examined the effects of regorafenib initiation timing (second-line versus third-line or later) and dosage (80 mg vs 120-160 mg) on PFS.
Results:
The triple therapy group demonstrated significantly superior efficacy compared to the dual therapy group. After PSM, the TRP group showed significantly improved median PFS (6.5 vs. 4.6 months) and OS (15.8 vs. 12.1 months), along with significantly higher ORR (32.8% vs. 17.2%) and DCR (.71.9% vs. 51.6%) compared to the TR group. Earlier regorafenib initiation (second-line) was associated with substantially prolonged PFS in both treatment arms (TRP group: 7.2 vs 5.1 months; TR group: 5.1 vs 4.2 months), whereas dosage variations did not significantly affect survival outcomes. TRAEs were comparable between groups except for a higher incidence of rash in the triple therapy group (25.0% vs 6.3%).
Conclusions:
The triple combination of TACE, regorafenib, and PD-1 inhibitors demonstrated superior clinical efficacy compared with TACE-regorafenib dual therapy in advanced HCC patients after targeted therapy failure, with optimal outcomes observed following earlier regorafenib initiation and an acceptable safety profile.
Insights
Triple therapy combining transarterial chemoembolization (TACE), regorafenib, and PD-1 inhibitors significantly improves outcomes for advanced hepatocellular carcinoma (HCC) patients post-targeted therapy. Earlier regorafenib initiation further enhances progression-free survival with manageable side effects.
Area of Science:
- Hepatobiliary Cancers
- Medical Oncology
- Immunotherapy
Background:
- Advanced hepatocellular carcinoma (HCC) after targeted therapy has limited options.
- Regorafenib is a standard second-line treatment, but its combination therapies need real-world validation.
- Optimizing treatment timing and dosing for combined therapies is crucial.
Purpose of the Study:
- To evaluate the efficacy and safety of combining transarterial chemoembolization (TACE) with regorafenib and PD-1 inhibitors in advanced HCC.
- To compare this triple therapy (TRP) against dual therapy (TACE + regorafenib).
- To assess the impact of regorafenib initiation timing and dosage on outcomes.
Main Methods:
- Retrospective, multicenter study of 188 HCC patients (BCLC B/C) post-targeted therapy failure.
- Propensity score matching (PSM) created comparable groups: 64 patients in triple therapy (TRP) and 64 in dual therapy (TR).
- Primary endpoints: progression-free survival (PFS) and overall survival (OS); Secondary: objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs).
Main Results:
- Triple therapy (TRP) showed significantly better median PFS (6.5 vs. 4.6 months) and OS (15.8 vs. 12.1 months) post-PSM.
- TRP achieved higher ORR (32.8% vs. 17.2%) and DCR (71.9% vs. 51.6%) compared to dual therapy.
- Second-line regorafenib initiation significantly improved PFS in both arms; dosage did not significantly impact survival. Rash was more frequent in the TRP group.
Conclusions:
- Combining TACE, regorafenib, and PD-1 inhibitors is superior to TACE-regorafenib dual therapy for advanced HCC after targeted therapy failure.
- Earlier initiation of regorafenib (second-line) is associated with improved PFS.
- This triple combination offers an acceptable safety profile with enhanced clinical efficacy.
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