The efficacy and safety of tislelizumab with or without tyrosine kinase inhibitor as adjuvant therapy in hepatocellular carcinoma with high-risk of recurrence after curative resection.

Background: Multiple studies have demonstrated that adjuvant therapy with programmed death-1 (PD-1) inhibitors can enhance the recurrence-free survival of patients with hepatocellular carcinoma (HCC) following curative resection. This study aims to assess the efficacy and safety of adjuvant tislelizumab (a PD-1 inhibitor), with or without tyrosine kinase inhibitors, in HCC patients at high risk of recurrence. Methods: This is a retrospective, multicenter, single-arm study that enrolled patients with high-risk factors for HCC recurrence. Within 4 to 8 weeks following curative resection, participants received tislelizumab, with or without tyrosine kinase inhibitors, as adjuvant therapy until disease recurrence, unacceptable toxicity, or a maximum of 1 year. The primary endpoint was recurrence-free survival. Secondary endpoints included overall survival and adverse events. Results: Between June 2020 and January 2024, a total of 108 patients were enrolled in the study. With a median follow-up duration of 24.3 months, the 12 - month and 24 - month recurrence-free survival rates were71.3% and 59.3%, respectively. The 12 - month and 24 - month overall survival rates were 88.0% and 83.4%, respectively, and the median recurrence-free survival and median overall survival were not reached. Among these 108 patients, 43 patients (39.8%) received tislelizumab monotherapy, while 65 patients (60.2%) received tislelizumab plus tyrosine kinase inhibitors. For both groups, the median recurrence-free survival (hazard ratio 1.46, 95%CI 0.58-1.90) and median overall survival (hazard ratio 1.06, 95%CI 0.42-2.67) were not reached, with no significant difference between the two groups. Patients who received adjuvant therapy for a duration of more than 6 months had a significantly longer median recurrence-free survival compared to those who received adjuvant therapy for less than 6 months (not reached vs. 22 months, hazard ratio 2.29, 95%CI 1.14-4.61). Although there was no significant difference in overall survival between the two groups (hazard ratio 2.59, 95%CI 0.80-8.35), the overall survival tended to be higher in the group with an adjuvant therapy duration of more than 6 months. The incidence of all treatment-related adverse events and that of grade 3 or higher was 79.6% and 30.6%, respectively. Conclusion: For patients with high-risk HCC, postoperative adjuvant therapy employing tislelizumab for a duration exceeding 6 months may represent a viable strategy for reducing the risk of tumor recurrence.