Conversion therapy downstages tumors and renders patients with unresectable hepatocellular carcinoma (HCC) eligible for radical resection. This study aimed to evaluate the efficacy and safety of tislelizumab plus lenvatinib and hepatic artery infusion chemotherapy with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4-HAIC) as a first-line conversion therapy.

Clinical data from HCC patients who were treated with the triple therapy between April 2021 and April 2022 were retrospectively analyzed. The primary outcome included objective response rate (ORR), disease control rate (DCR), conversion resection rate (CRR), and treatment-related adverse events (TRAEs).

A total of 18 patients completed conversion therapy assessment, which ended on March 27, 2023. The patients had a median age of 55.5 (37–72) years, and 94.4% were male. According to mRECIST, tumor shrinkage was observed in all patients, with an ORR of 94.4% (17/18), a DCR of 94.4% (17/18), and a median time to response of 1.4 (0.7–3.0) months. Successful conversion was observed in 61.1% (11/18) of patients (mRECIST). The CRR and pathological complete response were 38.9% (7/18) and 57.1% (4/7), respectively. The median progression-free survival (PFS) was 17.8 months, while median overall survival was not reached. The 6-and 9-month PFS rates were 83.3% and 66.7%, respectively. The most common TRAE (16/18 patients, 88.9%) was an increase in aspartate aminotransferase levels.

Tislelizumab combined with lenvatinib and FOLFOX4-HAIC achieved a high conversion rate and acceptable toxicity in patients with unresectable HCC, suggesting that this combination may represent a new conversion strategy for this population.