Hepatobiliary Pancreatic Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
School of Medicine, Tsinghua University, Beijing, China.
Front Immunol. 2023 Aug 30;14:1235724. doi: 10.3389/fimmu.2023.1235724. eCollection 2023.
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.
由于目前一线化疗方案的疗效有限，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）、仑伐替尼和程序性细胞死亡蛋白-1（PD-1）抑制剂联合治疗已广泛应用于晚期肝细胞癌的治疗，但它们在晚期 CCA 中的作用仍知之甚少。本研究旨在比较 HAIC 加仑伐替尼联合或不联合 PD-1 抑制剂治疗晚期 CCA 患者的疗效和安全性。
2019 年 3 月至 2022 年 6 月，对接受 HAIC 加仑伐替尼联合或不联合 PD-1 抑制剂治疗的晚期 CAA 患者进行回顾性分析，以评估其纳入标准。根据生存和肿瘤反应评估疗效，根据不良反应（AE）发生率评估安全性。
本研究共纳入 55 例晚期 CCA 患者，分为 HAIC+lenvatinib（LEN）+PD-1 抑制剂（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 组患者的无进展生存期（PFS）（HR=0.390；95%CI 0.189-0.806；p=0.001）和总生存期（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均高于 HAIC+LEN 组，但差异无统计学意义。HAIC+LEN+PD-1i 组 1-2 级和 3-4 级 AE 的发生率与 HAIC+LEN 组相比无显著升高，而 HAIC+LEN+PD-1i 组有 2 例（5.7%）患者发生 5 级免疫介导性肺炎。
HAIC 联合仑伐替尼加 PD-1 抑制剂安全且耐受良好，有可能延长晚期 CCA 患者的生存时间。联合 PD-1 抑制剂可能增强 HAIC 和仑伐替尼的疗效。因此，联合治疗有可能成为晚期 CCA 的治疗选择。
