Adjuvant HAIC combined with anlotinib and TQB2450 for resected high-risk hepatocellular carcinoma

Abstract

In this single-arm, phase 2 study, we explored the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anlotinib and TQB2450 (an anti-PD-L1 antibody) as a postoperative adjuvant treatment in patients at high risk of hepatocellular carcinoma (HCC) recurrence. Patients with high-risk recurrence of HCC were treated with HAIC, anlotinib (4 or 8 cycles), and TQB2450 after curative surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints included overall survival (OS) and safety. 77 patients who met the inclusion criteria were enrolled: 38 in the 4-cycle cohort and 39 in the 8-cycle cohort. As of the data cutoff on June 24, 2024, the median follow-up period was 21.19 months (95% confidence interval [CI], 20.49-21.89). The median DFS and OS of all patients were not reached. 1-year and 2-year DFS rates were 84.4% and 65.8%, respectively, while 1-year and 2-year OS rates were 96.1% and 89.8%, respectively. No significant differences in DFS and OS were observed in patients treated with 4 or 8 cycles of anlotinib. The incidence of grade 3/4 adverse events (AEs) was 28.6%. Postoperative adjuvant HAIC combined with anlotinib and TQB2450 demonstrated encouraging clinical benefits in reducing recurrence with manageable toxicities in patients at high risk of HCC recurrence. 4-cycle anlotinib combined with HAIC and TQB2450 is recommended as an adjuvant treatment for further investigation.

Keywords: TQB245; adjuvant therapy; anlotinib; hepatic arterial infusion chemotherapy; hepatocellular carcinoma; recurrence.

Graphical abstract

Figure 1

Flow diagram of the study A total of 102 patients were screened, and 25 were excluded (18 did not meet eligibility criteria, 5 withdrew consent, and 2 for other reasons). The remaining 77 patients were divided into two cohorts: the 4-cycle cohort (HAIC once + anlotinib for 4 cycles + TQB2450 for 4 cycles) and the 8-cycle cohort (HAIC once + anlotinib for 8 cycles + TQB2450 for 4 cycles). HAIC, hepatic arterial infusion chemotherapy; anlotinib, a multi-target tyrosine kinase inhibitor (TKI); TQB2450, an anti-PD-L1 antibody.

Figure 2

Kaplan-Meier curves for survival outcomes (A) DFS of all patients. The median DFS was not reached, with 1-year and 2-year DFS rates of 84.4% and 65.8%, respectively. (B) OS of all patients. The median OS was not reached, with 1-year and 2-year OS rates of 96.1% and 89.8%, respectively. (C) Comparison of DFS between the 4-cycle and 8-cycle cohorts. The median DFS was not reached in either cohort, with no significant difference between groups (p = 0.590). (D) Comparison of OS between the 4-cycle and 8-cycle cohorts. The median OS was not reached in either cohort, with no significant difference between groups (p = 0.774). DFS, disease-free survival; OS, overall survival.