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

Ning Peng¹Lin-Feng Mao¹Jia-Yong Su²Shao-Ping Liu³Jun-Jie Ou⁴Shu-Chang Chen⁴Ze Su⁵Wen-Feng Li⁶Fu-Quan Yang⁶Yong-Heng Zhou¹Le Li²Jian-Hong Zhong^2*

• ¹First Affiliated Hospital, Guangxi Medical University, Nanning, China
• ²Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Region, China
• ³Guigang City People's Hospital, Guigang, China
• ⁴Wuzhou People's Hospital, Wuzhou, China
• ⁵First People's Hospital of Nanning, Nanning, Guangxi Zhuang Region, China
• ⁶The First People’s Hospital of Yulin, Yulin, Shaanxi Province, China

Background: This study aims to assess the efficacy and safety of adjuvant tislelizumab, 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 inhibitorsTKIs, 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 ( [HR] 1.46, 95%CI 0.58 -1.90) and median overall survival (HR 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 recurrencefree survival compared to those who received adjuvant therapy for less than 6 months (not reached vs. 22 months, HR 2.29, 95% CI 1.14 -4.61).Although there was no significant difference in overall survival between the two groups (HR 2.59, 95% CI 0.80 --8.35, p = 0.112), the overall survival tended to be higher in the group with an adjuvant therapy duration of more than 6 4 / 23 months. The incidence of all treatment --related adverse events and that of grade 3 or higher was 79.6% and 30.6%, respectively.For patients with high-risk HCC, postoperative adjuvant therapy employing tislelizumab for a duration exceeding 6 months, either in combination with or without the use of TKIs, may represent a viable strategy for reducing the risk of tumor recurrence.