因当前一线化疗方案的有限疗效，需要新的治疗策略来改善晚期胆管癌（CCA）患者的预后。虽然肝动脉灌注化疗（HAIC）、利凡替尼和程序化细胞死亡蛋白-1（PD-1）抑制剂的联合应用在治疗晚期肝细胞癌方面已经得到广泛评估，但它们在晚期胆管癌的作用仍不明确。本研究的目的是比较HAIC加利凡替尼联合PD-1抑制剂与没有PD-1抑制剂的患者的疗效和安全性。 从2019年3月至2022年6月，回顾了接受HAIC加利凡替尼联合PD-1抑制剂治疗或没有PD-1抑制剂治疗的晚期胆管癌患者进行符合条件的评估。根据生存率和肿瘤反应评估疗效，根据不良事件（AE）发生率评估安全性。 本研究纳入了55例晚期胆管癌患者，分为HAIC+LEN+PD-1i组（n = 35）和HAIC+LEN组（n = 20）。中位随访时间为14.0（5-42）个月。HAIC+LEN+PD-1i组的PFS（HR = 0.390，95% CI 0.189-0.806，p = 0.001）和OS（HR = 0.461，95% CI 0.229-0.927，p = 0.01）明显优于HAIC+LEN组。HAIC+LEN+PD-1i组的客观缓解率和疾病控制率高于HAIC+LEN组，但没有显著差异。与HAIC+LEN组相比，HAIC+LEN+PD-1i组的1-2级和3-4级AE的发生率并没有显著增高，但HAIC+LEN+PD-1i组有2名患者（5.7%）出现了5级免疫介导性肺炎。 HAIC加利凡替尼联合PD-1抑制剂安全耐受，并有可能延长晚期胆管癌患者的生存时间。PD-1抑制剂的加入可能增强了HAIC和利凡替尼的疗效。因此，联合治疗可能成为晚期胆管癌的治疗选择。 版权所有© 2023 Wei, Wang, Wu, Liu, Wang, Ren, Yang, Chen and Zhang.

New treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA.Between March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs).Fifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5-42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia.HAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.Copyright © 2023 Wei, Wang, Wu, Liu, Wang, Ren, Yang, Chen and Zhang.