Huang Xiao-Yong, Shi Guo-Ming, Zheng Zhi-Tao, Sun Hui-Chuan, Liang Fei, Ji Yuan, Chen Yi, Yang Guo-Huan, Hu Zhi-Qiang, Lu Jia-Cheng, Meng Xian-Long, Guo Xiao-Jun, Zhang Chao-Chen, Fan Jia, Zhou Jian
Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.
Department of Statistics, Zhongshan Hospital, Fudan University, Shanghai, China.
BMC Med. 2025 Oct 21;23(1):573. doi: 10.1186/s12916-025-04404-4.
This research aimed to assess the efficacy and safety of a regimen combining lenvatinib with an anti-PD-1 antibody or chemotherapy in patients with advanced intrahepatic cholangiocarcinoma (ICC).
A two-arm, open-label, phase II trial was carried out. Participants in Arm A received 240 mg of toripalimab intravenously on day 1 of each 3-week cycle, plus daily oral lenvatinib at 8 mg (< 60 kg) or 12 mg (≥60 kg). Participants in Arm B were administered the same daily lenvatinib in combination with GEMOX chemotherapy: 85 mg/m oxaliplatin on day 1, and 1 g/m gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS).
Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3% (10/31; 95% CI: 16.7%-51.4%), and three patients underwent surgery after tumor downstaging. The median OS was 20.3 months (95% CI: 9.3-27.1), and median PFS was 8.9 months (95% CI: 4.2-13.9). Arm B showed an ORR of 40.0% (12/30; 95% CI: 22.7%-59.4%), and one patient proceeded to surgery after downstaging. Median OS was 15.5 months (95% CI: 9.6-23.8), and median PFS was 8.0 months (95% CI: 5.0-11.4). Adverse events (AEs) related to treatment were observed in most patients, with grade 3-4 AEs in 35.5% of Arm A and 40.0% of Arm B. The most frequent AEs were fatigue (71% vs. 63%), paresthesia (45% vs. 40%), and gingivitis (45% vs. 20%). Grade 4 thrombocytopenia occurred in 6.7% of Arm B. No grade 5 AEs were observed. Peripheral blood analysis showed monocyte levels decreased in PR(partial response) patients in Arm A but increased in PR patients in Arm B.
The Combination of lenvatinib with either anti-PD-1 antibody or GEMOX chemotherapy is a well-tolerated and effective treatment for advanced ICC.
ClinicalTrials.gov, NCT04361331.
本研究旨在评估乐伐替尼联合抗程序性死亡蛋白1（PD-1）抗体或化疗方案治疗晚期肝内胆管癌（ICC）患者的疗效和安全性。
开展了一项双臂、开放标签的II期试验。A组参与者在每3周周期的第1天静脉注射240mg托瑞帕利单抗，同时每日口服乐伐替尼，体重<60kg者剂量为8mg，体重≥60kg者剂量为12mg。B组参与者接受相同剂量的每日口服乐伐替尼联合GEMOX化疗：每3周的第1天静脉注射奥沙利铂85mg/m²，第1天和第8天静脉注射吉西他滨1g/m²，共进行6-8个周期。主要终点是根据实体瘤疗效评价标准（RECIST）1.1版评估的客观缓解率（ORR），次要终点包括治疗相关不良事件（AE）、总生存期（OS）和无进展生存期（PFS）。
共招募61例患者，A组31例，B组30例。A组的ORR为32.3%（10/31；95%CI：16.7%-51.4%），3例患者在肿瘤降期后接受了手术。中位OS为20.3个月（95%CI：9.3-27.1），中位PFS为8.9个月（95%CI：4.2-13.9）。B组的ORR为40.0%（12/30；95%CI：22.7%-59.4%），1例患者在降期后接受了手术。中位OS为15.5个月（95%CI：9.6-23.8），中位PFS为8.0个月（95%CI：5.0-11.4）。大多数患者观察到治疗相关不良事件，A组35.5%、B组40.0%的患者发生3-4级AE。最常见的AE为疲劳（71%对63%）、感觉异常（45%对40%）和牙龈炎（45%对20%）。B组6.7%的患者发生4级血小板减少。未观察到5级AE。外周血分析显示，A组部分缓解（PR）患者的单核细胞水平下降，而B组PR患者的单核细胞水平升高。
乐伐替尼联合抗PD-1抗体或GEMOX化疗是晚期ICC耐受性良好且有效的治疗方案。
ClinicalTrials.gov，NCT04361331
