Transarterial chemoembolization combined with lenvatinib and sintilimab vs lenvatinib alone in intermediate-advanced hepatocellular carcinoma

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that has limited treatment options and a poor prognosis. Transarterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia, thereby promoting angiogenesis. Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might improve efficacy. Lenvatinib, a tyrosine kinase inhibitor, has demonstrated superior outcomes compared to sorafenib, while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE. However, the efficacy and safety of TACE combined with lenvatinib and sintilimab (TACE + SL) compared to TACE with lenvatinib alone (TACE + L) in patients with intermediate-advanced HCC has not yet been investigated.

AIM

To evaluate the efficacy and safety of TACE + SL therapy in comparison to TACE + L therapy in patients with intermediate-advanced HCC.

METHODS

A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022. Baseline characteristics were compared, and propensity score matching was applied. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were evaluated between the two groups, and adverse events were analyzed.

RESULTS

The study included 57 patients, with 30 in the TACE + SL group and 27 in the TACE + L group. The TACE + SL group demonstrated significantly improved median PFS and OS compared to the TACE + L group (PFS: 14.1 months vs 9.6 months, P = 0.016; OS: 22.4 months vs 14.1 months, P = 0.039), along with a higher ORR (70.0% vs 55.6%). After propensity score matching, 30 patients were included, with the TACE + SL group again showing longer median PFS and a trend toward improved OS (PFS: 14.6 months vs 9.2 months, P = 0.012; OS: 23.9 months vs 16.3 months, P = 0.063), and a higher ORR (73.3% vs 53.3%). No severe adverse events were reported.

CONCLUSION

TACE + SL demonstrated superior outcomes in terms of OS and PFS, compared to TACE + L. These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.

Keywords: Hepatocellular carcinoma; Transarterial chemoembolization; Sintilimab; Lenvatinib; Immunotherapy; Programmed cell death 1; Prognosis

Core Tip: This study evaluates the efficacy and safety of combining transarterial chemoembolization (TACE) with lenvatinib and sintilimab compared to TACE with lenvatinib alone in patients with intermediate-advanced hepatocellular carcinoma. The results indicate that TACE with lenvatinib and sintilimab significantly improves overall survival (22.4 months vs 14.1 months) and progression-free survival (14.1 months vs 9.6 months), with a higher objective response rate (70% vs 55.6%). Notably, no severe adverse events were reported, suggesting that the combination therapy is effective and safe. These findings support the inclusion of sintilimab in hepatocellular carcinoma treatment regimens.