背景：在II期临床试验中，程序性细胞死亡蛋白-1（PD-1）抑制剂联合lenvatinib和Gemox化疗作为一线疗法显示出高抗肿瘤活性抗胆道癌。在这里，我们旨在通过一项多中心真实世界研究,探讨晚期肝内胆管癌(ICC)的疗效和安全性.
方法：在两个医疗中心对接受PD-1抑制剂联合lenvatinib和Gemox化疗的晚期ICC患者进行回顾性筛查。主要终点是总生存期（OS）和无进展生存期（PFS），而次要终点是客观反应率（ORR），疾病控制率（DCR），和安全。分析影响生存的预后因素。
结果：本研究纳入了53例晚期ICC患者。中位随访时间为13.7个月（95％置信区间（CI）：12.9-17.2）。中位OS和PFS分别为14.3个月(95%CI:11.3-NR)和8.63个月(95%CI:7.17-11.6),分别。ORR,DCR,临床获益率分别为52.8%、94.3%和75.5%，分别。在多变量分析中，肿瘤负荷评分（TBS），肿瘤淋巴结转移分类（TNM）分期，PD-L1表达是OS和PFS的独立预后因素。所有患者均出现不良事件（AE），41.5%(22/53)经历过3级或4级不良事件，包括疲劳（8/53，15.1%）和骨髓抑制（7/53，13.2%）。未报告5级AE。
结论：PD-1抑制剂联合lenvatinib和Gemox化疗在一项多中心回顾性真实世界研究中代表了晚期ICC的有效和可耐受方案。TBS,TNM阶段,PD-L1表达可作为OS和PFS的潜在预后因素。
BACKGROUND: A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world
study.
METHODS: Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed.
RESULTS: Fifty-three patients with advanced ICC were included in this
study. The median follow-up time was 13.7 (95% confidence interval (CI): 12.9-17.2) months. The median OS and PFS were 14.3 (95% CI: 11.3-NR) and 8.63 (95% CI: 7.17-11.6) months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, and 75.5%, respectively. In the multivariate analysis, the tumor burden score (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression were independent prognostic factors for OS and PFS. All patients experienced adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were reported.
CONCLUSIONS: PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy represent an effective and tolerable regimen for advanced ICC in a multicenter retrospective real-world
study. TBS, TNM stage, and PD-L1 expression can be used as potential prognostic factors for OS and PFS.
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