Abstract
BACKGROUND: Previous LAUNCH trial revealed the promising effectiveness of transarterial chemoembolization (TACE) combined with lenvatinib for advanced hepatocellular carcinoma (HCC). However, most intermediate-stage HCC exceeds the up-to-seven criteria, limiting their potential TACE benefits. Hepatic arterial infusion chemotherapy (HAIC) was widely endorsed for delivering substantial survival benefits for high tumor burden HCC, outperforming TACE. Accordingly, we undertook this study to evaluate the efficacy and safety of TACE combined with HAIC plus lenvatinib for intermediate-stage HCC beyond up-to-seven criteria. METHODS: From June 2017 to November 2021, clinical data of intermediate-stage HCC patients beyond up-to-seven criteria received TACE combined with HAIC plus lenvatinib or TACE alone from four medical centers in China were retrospectively collected. Propensity score matching (PSM) and inverse probability weighting (IPTW) were applied to balance baseline differences. The Kaplan-Meier method was utilized for survival analysis. Cox regression-based multivariate analysis was used to identify survival-related risk factors. We compare tumor response and the incidence of adverse reactions between groups. RESULTS: A total of 294 intermediate-stage HCC patients beyond up-to-seven criteria received TACE combined with HAIC plus lenvatinib (the TACEHL group, n = 127) or TACE monotherapy (the TACE group, n = 167) were finally enrolled. Following propensity matching, the median OS and median PFS in the TACEHL group were 34.6 months and 15.7 months, respectively, significantly higher than the 15.7 months and 6.9 months observed in the TACE group. In tumor response, the ORR was 71.4% in the TACEHL group and 30.8% in the TACE group (P < 0.001), the DCR was 92.3% in the TACEHL group and 75.8% in the TACE group (P = 0.005). The 3-4 grade adverse reactions were comparable between the groups. CONCLUSION: For intermediate-stage HCC beyond up-to-seven criteria, the integration of TACE and HAIC plus lenvatinib therapy demonstrated substantial enhancements in survival prognosis, which is a promising treatment regimen.