Sintilimab combined with lenvatinib versus hepatic artery infusion chemotherapy (HAIC) for neoadjuvant treatment of resectable primary hepatocellular carcinoma with high risk of recurrence: A prospective, two-arm, randomized, phase II clinical study.

e16301 Background: The high recurrence rate after resection is closely associated with poor prognosis for resectable hepatocellular carcinoma (HCC). There is no standard of care neoadjuvant therapy. HAIC or the combination of lenvatinib and anti-PD-1 antibodies has shown better trend in tumor response and survival outcomes on unresectable HCC. This study aims to compare the safety and efficacy of lenvatinib combined with sintilimab versus HAIC as neoadjuvant therapy for resectable HCC with high recurrence risk. Methods: This prospective, two-arm, randomized, phase II clinical study (NCT05519410) enrolled patients (pts) with resectable primary HCC who met at least one of the following risk factors, as assessed by the investigators before surgery: CNLC stage Ib (2-3 tumors with a maximum diameter ≤ 3 cm) or CNLC stage IIa (2-3 tumors, with the largest having a diameter > 3 cm). Pts with ECOG 0-1, Child Pugh A, and without prior anti-tumor treatment had at least one measurable lesion. Eligible pts were randomly assigned to receive sintilimab 200 mg Q3W and lenvatinib 8 mg QD for 2 cycles (S+L) or HAIC-FOLFOX for 2 cycles (HAIC), and surgery was performed within 3-4 weeks after treatment. The primary endpoint was 1-year disease-free survival (DFS) rate. Secondary endpoints were objective response rate (ORR, by RECIST v1.1), percentage of microvascular invasion, pathological complete response (pCR) rate, 2-year DFS and OS rate and safety. Results: Until December 31, 2024, a total 46 pts were enrolled. However, 6 pts were excluded due to refusal of resection (3 pts) or protocol violations (3 pts). The remaining 40 pts were randomly (1:1) allocated to receive neoadjuvant S+L or HAIC. At the cutoff date, 2 pts in S+L group and 1 in HAIC group were still undergoing treatment. Radiological evaluations were conducted for 37 pts (S+L, n = 18; HAIC, n = 19). ORR based on RECIST v1.1 and mRECIST were 0% and 38.9% in S+L group, 5.3% and 21.1% in HAIC group, respectively. All 37 pts underwent radical resection, the pCR rates were 5.8% (1/18) in S+L group while no pts achieved complete pathological response in HAIC group. No grade 3 or higher TREAs occurred in both groups. Conclusions: For resectable HCC pts with CNLC stage Ib (2-3 tumors with a maximum diameter ≤ 3 cm) or CNLC stage IIa (2-3 tumors, with the largest having a diameter > 3 cm), the safety of neoadjuvant therapy with HAIC or sintilimab combined with lenvatinib was comparable. Given that the current data on disease free survival are not yet mature, the efficacy of these two groups were unclear. Clinical trial information: NCT05519410 .