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Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular
Hai-Dong Zhu1, Hai-Liang Li2, Ming-Sheng Huang3
1Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
Abstract:
There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
Insights
Combining transarterial chemoembolization (TACE) with PD-(L)1 inhibitors and molecular targeted treatments (MTT) significantly improves progression-free survival (PFS) and overall survival (OS) in advanced hepatocellular carcinoma (HCC). This combination therapy demonstrates a higher objective response rate (ORR) with an acceptable safety profile compared to TACE monotherapy.
Area of Science:
- Hepatocellular Carcinoma (HCC) Treatment Strategies
- Oncology
- Interventional Radiology
Background:
- Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide.
- Integrating transarterial chemoembolization (TACE) with novel systemic therapies like PD-(L)1 inhibitors and molecular targeted treatments (MTT) shows potential for improved HCC management.
- Real-world evidence is crucial to evaluate the efficacy and safety of such combination regimens.
Purpose of the Study:
- To investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in a real-world setting for HCC patients.
- To compare outcomes between a combination therapy group and TACE monotherapy group.
Main Methods:
- Nationwide, retrospective cohort study including 826 HCC patients (January 2018 - May 2021).
- Patients received either TACE plus PD-(L)1 inhibitors and MTT (combination group, n=376) or TACE monotherapy (monotherapy group, n=450).
- Propensity score matching was employed to minimize bias, resulting in 228 matched pairs, predominantly with advanced HCC.
Main Results:
- The combination group showed significantly improved median progression-free survival (PFS) (9.5 months vs. 8.0 months; adjusted HR, 0.70; P=0.002).
- Overall survival (OS) and objective response rate (ORR) were also significantly higher in the combination group (median OS: 19.2 vs. 15.7 months; ORR: 60.1% vs. 32.0%; P<0.001).
- Grade 3/4 adverse events occurred more frequently in the combination group (15.8%) compared to the monotherapy group (7.5%).
Conclusions:
- TACE combined with PD-(L)1 inhibitors and MTT offers significant improvements in PFS, OS, and ORR compared to TACE monotherapy for advanced HCC in Chinese real-world practice.
- The combination therapy demonstrates an acceptable safety profile despite a higher incidence of severe adverse events.
- This multimodal approach represents a promising treatment strategy for advanced HCC.
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