Huang Jia-Xin, Liu Bo, Li Yu, Li Xi, Ding Li-Juan, Wang Nan-Ya
Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Front Oncol. 2023 Aug 18;13:1204486. doi: 10.3389/fonc.2023.1204486. eCollection 2023.
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients.
This retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan-Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events.
The median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0-72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group ( = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group ( = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312-8.746, = 0.012) and OS (HR = 4.220, 95% CI = 1.131-15.742, = 0.032).
PD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.
肝内胆管癌（ICC）是一种侵袭性很强的原发性肝癌，在全球范围内发病率呈上升趋势。目前，晚期ICC患者有效的一线治疗方法有限。因此，我们的研究旨在评估程序性死亡受体1（PD-1）/程序性死亡配体1（PD-L1）抑制剂联合吉西他滨/顺铂（GC）和乐伐替尼作为晚期ICC患者一线治疗的疗效和安全性。
这项回顾性队列研究纳入了51例晚期ICC患者，其中25例患者接受PD-1/PD-L1联合乐伐替尼治疗，26例患者接受PD-1/PD-L1联合GC治疗。收集了包括人口统计学信息、病史、临床特征、实验室数据和影像学检查在内的基线特征。主要终点为无进展生存期（PFS）以及第六个月和第九个月的总生存期（OS）率。采用Kaplan-Meier法绘制生存曲线。进行Cox比例风险模型以研究PFS和OS的独立危险因素。次要结局为客观缓解率（ORR）、疾病控制率（DCR）和不良事件。
我们研究中晚期ICC患者的中位年龄为58.0岁（95%置信区间[95%CI]=48.0-72.4），男性33例，女性18例。PD-1/PD-L1抑制剂联合乐伐替尼组的患者更有可能ECOG评分高于1、出现腹水且谷丙转氨酶水平升高。PD-1/PD-L1抑制剂联合乐伐替尼组的ORR为16.0%，GC组为23.1%（P=0.777）。乐伐替尼组的DCR为52.0%，GC组为46.2%（P=0.676）。PD-1/PD-L1抑制剂联合乐伐替尼的联合治疗与GC组相比，PFS更长；然而，差异无统计学意义（乐伐替尼组：9.5个月，GC组：5.1个月，P=0.454）。乐伐替尼组第六个月和第九个月的OS率分别为82.0%和76.9%，GC组分别为87.4%和71.5%。在调整混杂因素后，多因素Cox回归分析显示，ECOG评分高于1是PFS（风险比[HR]=3.388，95%CI=1.312-8.746，P=0.012）和OS（HR=4.220，95%CI=1.131-15.742，P=0.032）的独立危险因素。
PD-1/PD-L1抑制剂联合乐伐替尼或GC作为晚期ICC患者的一线治疗均显示出显著的疗效和安全性。对于拒绝或不耐受化疗的患者，建议使用PD-1/PD-L1联合乐伐替尼。
