Clinical and biomarker analyses of hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitor for patients with advanced intrahepatic cholangiocarcinoma

• DOI: 10.3389/fimmu.2024.1260191
• Publication Date: 2024-02-07T12:31:25Z
• Authors: YeXing Huang; ZeFeng Du; Anna Kan; MinKe He; HuiFang Li; ZhiCheng Lai; DongSheng Wen; LiChang Huang; QiJiong Li; Li Xu; Ming Shi
• Keywords: Lenvatinib; Clinical endpoint; Intrahepatic Cholangiocarcinoma; FOLFOX; Progression-free survival

Background Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination lenvatinib PD-1 inhibitor for patients advanced iCCA. Methods Locally or metastatic iCCA receiving triple therapy lenvatinib, inhibitor, FOLFOX-HAIC were included this retrospective study. Primary endpoint was progression-free survival, evaluated using RECIST criterion. The secondary endpoints overall objective response rate, safety. Whole exome RNA sequencing tumor biopsy tissues performed biomarker exploration. Results Between May, 2019 December 2022, total 46 primary showed median survival 9.40 months (95% CI: 5.28-13.52), 6-month rate 76.1%. 16.77 CI, 14.20-19.33), an 47.8% disease control 91.3% per RECIST. In addition, 4.3% 8.7% achieved complete all lesions intrahepatic target mRECIST, respectively. most common treatment-related adverse events neutropenia, thrombocytopenia, elevated aspartate aminotransferase alanine level. Furthermore, integrated analysis genetic, transcriptomic, immunohistochemistry data revealed that pre-existing immunity (high expression level immune-related signatures intra-tumoral CD8 + T cell density) baseline associated superior clinical benefits. However, evaluation mutation burden did not show potential value combination. Conclusion demonstrated promising antitumor activity manageable safety profiles Moreover, our also new perspectives on efficacy.