Safety and efficacy of HAIC or lenvatinib combined with sintilimab as neoadjuvant therapy for high recurrence risk resectable stage IB solitary hepatocellular carcinoma: A prospective, randomized, two-cohort, exploratory phase II clinical study.

Abstract

e16288 Background: PD-1/PD-L1 inhibitors combined with targeted agents or HAIC (Hepatic Arterial Infusion Chemotherapy) can reduce the burden of micrometastasis and improve clinical outcomes, which has shown promising efficacy as neoadjuvant therapy for resectable hepatocellular carcinoma (HCC). Combination regimens including immunotherapy are available for wider application due to the ease of implementation. This study aims to compare the safety and efficacy of lenvatinib combined with sintilimab versus HAIC as neoadjuvant therapy for resectable stage IB solitary hepatocellular carcinoma with high recurrence risk. Methods: This prospective, randomized, two-cohort, exploratory, phase II study (NCT05621499) enrolled patients with histologically confirmed resectable HCC. Patients with ECOG 0-1, Child Pugh A, and no prior treatment had at least one measurable lesion according to RECIST v1.1. The high risk of recurrence was defined by the investigators before surgery as stage Ib and solitary tumor with the largest diameter > 5cm. Eligible patients were randomly assigned to receive HAIC-FOLFOX for 2 cycles (Group 1, G1) or sintilimab 200 mg Q3W and lenvatinib 12 or 8 mg QD for 2 cycles (Group 2, G2), and surgery was performed within 2-3 weeks after treatment. The primary endpoint was 1-year disease-free survival (DFS) rate. Secondary endpoints were incidence of microvascular invasion, pathological complete response (pCR) rate, objective response rate (ORR, by RECIST v1.1), 2-year DFS rate, 2-year overall survival (OS) rate, and safety. Results: As of December 31, 2024, 54 patients were enrolled and assigned to G1 (n = 27) and G2 (n = 27). At the cutoff date, 5 patients in G1 and 6 patients in G2 were still receiving treatment. Two patients in G2 were excluded due to poor liver function. Radiological evaluations were conducted for 40 patients (G1, n = 21; G2, n = 19). According to RECIST v1.1 and mRECIST, the ORR was 9.52% and 23.81% in G1, 31.58% and 57.89% in G2, respectively. 39 patients (G1, n = 21; G2, n = 18) underwent radical resection and all achieved R0 resection. In terms of pathological outcomes, no patients achieved complete response in G1, the pCR rates were 33.33% (6/18) in G2. No grade≥3 adverse events were observed during neoadjuvant treatment period in either group. Conclusions: Sintilimab in combination with lenvatinib was well tolerated and showed promising efficacy compared with HAIC as a neoadjuvant therapy for high recurrence risk resectable stage IB solitary HCC. The data of DFS was immature, and follow-up is continuing. Clinical trial information: NCT05621499 .