Second-line systematic strategy options for the progression of lenvatinib plus tislelizumab treating unresectable hepatocellular carcinoma: A retrospective study.

e16135 Background: Lenvatinib plus Tislelizumab (LEN+TIS) is a first-line systemic treatment for unresectable hepatocellular carcinoma (uHCC) in the real world, however, most uHCC ultimately fail to respond to first-line therapy due to tumor progression or intolerable adverse effects. The progression-free survival (PFS) of Lenvatinib was approximately 8 months in both REFLECT and LEA-002 studies. Therefore, there were doubts about the second-line therapy after progressive disease (PD) of LEN+TIS, and no studies hade reported the specific switching mode. Methods: This study retrospectively analyzed the clinical data of the first-line treatment of uHCC with LEN+TIS in National Cancer Center/Cancer Hospital & Shenzhen Hospital from April 2019 to December 2023. According to the actual use of drugs, Group A changed Lenvatinib to Regorafenib while Tislelizumab was not changed after PD of LEN+TIS; Group B replaced with Regorafenib plus other immune checkpoint inhibitors (including PD-1, PDL-1) after PD of LEN+TIS. The initial dose of Regorafenib was 80 to 160 mg, which could be adjusted according to patient tolerability, with Regorafenib administered orally once daily for the first 3 weeks, every 4 weeks as a cycle; Tislelizumab given 200mg intravenously every 3 weeks. Both group A and B were subdivided into two subgroups based on whether PFS of LEN+TIS had been more than 8 months. Short- and long-term outcomes were assessed by two independent radiologists according to mRESCIST criteria, all statistical analysis was performed using SPSS version 20. Results: After rigorous screening, a total of 446 samples were recruited in this study, including 208 in group A and 238 in group B. The baseline characteristics were comparable between the two groups, all patients were Child-Pugh grade A, and the median follow-up time was 9.8 months. Group A had higher objective response rates (ORR: 31.2%vs26.9%), PFS (7.6vs6.1months), and median overall survival (mOS: 12.8vs11.2months). Subgroup analysis showed that patients in group A who had first-line PFS shorter than 8 months had a better treatment effect than those with first-line PFS longer than 8 months (ORR: 36.9%vs17.7%; DCR:69.2%vs46.8%;PFS: 8.7vs 5.1months; OS: 14.4vs8.9months; P<0.05); patients in group B who were treated with first-line systemic PFS shorter than 8 months was worse than that with first-line PFS longer than 8 months (ORR:12.2%vs38.6%; DCR:45.3%vs68.9%;PFS:5.6vs6.4months;OS:9.1vs12.6months; P<0.05). No new adverse events were observed, no treatment-related deaths occurred in either group. Conclusions: If the PFS of LEN+TIS was shorter than 8 months, Lenvatinib should be changed to Regorafenib, Tislelizumab could be not changed. And if the PFS of LEN+TIS was longer than 8 months, Lenvatinib and Tislelizumab should be changed at the same time, which seemed to achieve better results.