Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study

作者：Guo‐Ming Shi, Xiaoyong Huang, Dong Wu, Hui‐Chuan Sun, Fei Liang, Yuan Ji, Yi Chen, Guo‐Huan Yang, Jia‐Cheng Lu, Xian‐Long Meng, Xinying Wang, Lei Sun, Ningling Ge, Xiaowu Huang, Shuang-Jian Qiu, Xin‐Rong Yang, Qiang Gao, Yifeng He, Yang Xu, Jian Sun, Zhenggang Ren, Jia Fan, Jian Zhou · 发表于：Signal Transduction and Targeted Therapy · 年份：2023 · DOI：10.1038/s41392-023-01317-7 · 被引用次数：155 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Peptidase Inhibition and Analysis、Cancer Mechanisms and Therapy

Abstract Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m 2 ) on Days 1 and 8 and oxaliplatin (85 mg/m 2 ) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40....