Wang Shanshan, Chao Jiashuo, Wang Hao, Li Shuofeng, Wang Yunchao, Zhu Chengpei, Zhang Nan, Piao Mingjian, Yang Xu, Liu Kai, Xun Ziyu, Sang Xinting, Yang Xiaobo, Duan Weidong, Zhao Haitao
State Key Laboratory of Complex Severe and Rare Diseases, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
Organ Transplantation Center, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Cancer Immunol Immunother. 2024 Oct 3;73(12):249. doi: 10.1007/s00262-024-03841-z.
Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.
This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.
A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).
Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.
目前晚期肝内胆管癌（ICC）的治疗选择有限。含化疗方案是主要治疗方法，但伴有明显毒性、耐受性差和依从性降低，因此需要探索替代疗法。在初步研究中，乐伐替尼联合PD-1抑制剂已显示出显著的临床活性。本研究旨在评估乐伐替尼联合托瑞帕利单抗（一种新型PD-1抗体）作为晚期ICC无化疗疗法的有效性和安全性。
这项回顾性研究纳入了2019年2月至2023年12月期间连续接受乐伐替尼联合托瑞帕利单抗治疗的晚期ICC患者。主要结局指标为总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性。还进行了预后因素分析和基因改变的探索性分析。
共纳入78例患者，中位随访时间为25.9个月。中位OS和PFS分别为11.3（95%CI：9.5-13.1）个月和5.4（95%CI：3.8-7.0）个月。ORR为19.2%，DCR为75.6%。3级或4级不良事件（AE）的发生率为50.0%，未报告5级AE。基线CA19-9水平正常的患者ORR更高（p=0.011），PFS更长（11.5个月对4.6个月；HR 0.47；p=0.005），OS更长（21.0个月对9.7个月；HR 0.43；p=0.003）。IDH1突变的存在与ORR增加相关（60.0%对8.9%，p=0.016）。
乐伐替尼联合托瑞帕利单抗是晚期ICC一种有效且耐受性良好的无化疗治疗选择。基线CA19-9水平和IDH1突变可作为预测治疗相关生物标志物。
