Hepatic arterial infusion plus systemic chemotherapy, lenvatinib and PD- (L)1 inhibitors versus gemcitabine and cisplatin plus PD-(L)1 inhibitors in advanced intrahepatic cholangiocarcinoma

Huazhong Guo^1,2,3YeXing Huang^1,2,3Na Liu^1,2,3MinKe He^1,2,3Zhicheng Lai^1,2,3Shi Ming^1,2,3*Qijiong Li^1,2,3*

• ¹Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
• ²State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
• ³Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, Guangdong, China

Background: The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) remains poor and emerging evidence shows therapeutic efficacy of hepatic arterial infusion chemotherapy (HAIC) in ICC. This retrospective cohort study aims to investigate the efficacy and safety of HAIC plus systemic chemotherapy, lenvatinib and PD-(L)1 inhibitors in advanced ICC. Methods: Between April 2021 and July 2024, patients diagnosed with advanced ICC treated with HAIC of oxaliplatin plus systemic chemotherapy of gemcitabine, lenvatinib and PD-(L)1 inhibitors (HSLP) or systemic chemotherapy of gemcitabine and cisplatin plus PD-(L)1 inhibitors (SP) were consecutively enrolled in this study. The propensity score matching (PSM) was used to minimize selection bias. The primary endpoint was objective response rate (ORR) according to RECISTv1.1 criteria. Secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety. Results: A total of 110 patients were recruited in this study with 53 in HSLP group and 57 in SP group. Prior to PSM, the ORR was significantly higher in the HSLP group than in the SP group (47.2% vs. 24.6%; P = 0.023). OS and PFS were prolonged in the HSLP group compared to the SP group (median OS: 15.2 vs. 12.3 months, P = 0.002; median PFS: 11.3 vs. 7.3 months, P = 0.004). After 1:1 PSM, 37 patients were included in each group. The ORR remained significantly higher in the HSLP group (43.2% vs. 18.9%; P = 0.045). Similarly, both median OS (15.4 vs. 11.8 months, P = 0.018) and median PFS (11.9 vs. 6.9 months, P = 0.019) were longer in the HSLP group. Multivariate analysis identified the treatment regimen as an independent prognostic factor for OS and PFS. Among any-grade TRAEs, neutropenia was the most common in the HSLP group (62.2%), whereas anemia was more frequent in the SP group (64.9%). The incidence of grade 3–4 TRAEs was comparable between two groups. All treatment-related adverse events were manageable with supportive care, and no additional toxicities were observed in the HSLP group. Conclusion: HAIC plus systemic chemotherapy, lenvatinib and PD-(L)1 inhibitors represents a promising therapeutic regimen for advanced ICC patients, with tolerable