免疫相关不良反应与晚期胆管癌患者 PD-1 抑制剂联合治疗的疗效相关：一项回顾性队列研究。
Immune-related adverse events correlate with the efficacy of PD-1 inhibitors combination therapy in advanced cholangiocarcinoma patients: A retrospective cohort study.
机构信息
Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
出版信息
Front Immunol. 2023 Mar 24;14:1141148. doi: 10.3389/fimmu.2023.1141148. eCollection 2023.
BACKGROUND
Whether irAEs can predict the efficacy of PD-1 inhibitors in cholangiocarcinoma (CCA) has not been assessed. Therefore, this study aims to investigate the correlation between irAEs and the therapeutic effect of PD-1 inhibitors combination therapy in patients with advanced CCA.
METHODS
All patients with CCA who were consecutively admitted to the inpatient unit of our hospital and received PD-1 inhibitors combination therapy between September 2020 and April 2022 were screened. In total, 106 patients with CCA were screened out. We then followed up these patients until October 2022. Due to perioperative use (n=28), less than 2 cycles of PD-1 inhibitor therapy (n=9), incomplete data (n=8) and no pathological report (n=2), 59 patients were included in the final analysis. The patients were divided into the irAEs cohort and the non-irAEs cohort according to whether they experienced irAEs or not. The Log-Rank test was performed to compare the difference in survival time between these two cohorts. We then applied multivariate COX regression analysis to investigate whether irAEs were independent prognostic factors for survival in patients with advanced CCA.
RESULTS
Finally, 32 patients were included in the irAEs cohort and 27 patients in the non-irAEs cohort. A total of 32 patients (54.2%) had any-grade irAEs, of which 4 patients (6.8%) had grade 3-4 irAEs. The most common irAEs were thyroid toxicity (30.5%) and dermatologic toxicity (30.5%). There were no notable differences in demographics and clinical characteristics between the irAEs and non-irAEs cohorts, except for total bilirubin level (P=0.026) and relapse (P=0.016). The disease control rate (DCR) in the irAEs cohort was higher than in the non-irAEs cohort (90.6% vs 70.4%, P=0.047). Median overall survival (OS) and median progression-free survival (PFS) were better in the irAEs cohort than in the non-irAEs cohort (OS: 21.2 vs 10.0 months, P<0.001; PFS: 9.0 vs 4.4 months, P=0.003). Multivariate COX regression analysis showed that irAEs were independent prognostic factors for OS and PFS (OS: HR=0.133, 95% CI: 0.039-0.452, P=0.001; PFS: HR=0.435, 95% CI: 0.202-0.934, P=0.033).
CONCLUSION
IrAEs correlated with improved DCR, OS, and PFS in advanced CCA patients receiving PD-1 inhibitors combination therapy.
背景
免疫相关不良反应（irAEs）是否可以预测胆管癌（CCA）患者接受 PD-1 抑制剂治疗的疗效尚未得到评估。因此，本研究旨在探讨 irAEs 与晚期 CCA 患者接受 PD-1 抑制剂联合治疗的疗效之间的相关性。
方法
筛选 2020 年 9 月至 2022 年 4 月期间连续入住我院并接受 PD-1 抑制剂联合治疗的 CCA 患者。共筛选出 106 例 CCA 患者。然后对这些患者进行随访，直到 2022 年 10 月。由于围手术期使用（n=28）、PD-1 抑制剂治疗不足 2 个周期（n=9）、数据不完整（n=8）和无病理报告（n=2），最终有 59 例患者纳入最终分析。根据是否发生 irAEs，将患者分为 irAEs 队列和非 irAEs 队列。采用 Log-Rank 检验比较两组患者的生存时间差异。然后应用多变量 COX 回归分析探讨 irAEs 是否是晚期 CCA 患者生存的独立预后因素。
结果
最终，32 例患者纳入 irAEs 队列，27 例患者纳入非 irAEs 队列。共有 32 例（54.2%）患者发生任何级别的 irAEs，其中 4 例（6.8%）患者发生 3-4 级 irAEs。最常见的 irAEs 是甲状腺毒性（30.5%）和皮肤毒性（30.5%）。irAEs 队列和非 irAEs 队列之间除总胆红素水平（P=0.026）和复发（P=0.016）外，在人口统计学和临床特征方面无显著差异。irAEs 队列的疾病控制率（DCR）高于非 irAEs 队列（90.6% vs 70.4%，P=0.047）。irAEs 队列的中位总生存期（OS）和中位无进展生存期（PFS）均优于非 irAEs 队列（OS：21.2 与 10.0 个月，P<0.001；PFS：9.0 与 4.4 个月，P=0.003）。多变量 COX 回归分析显示，irAEs 是 OS 和 PFS 的独立预后因素（OS：HR=0.133，95%CI：0.039-0.452，P=0.001；PFS：HR=0.435，95%CI：0.202-0.934，P=0.033）。
结论
irAEs 与晚期 CCA 患者接受 PD-1 抑制剂联合治疗的 DCR、OS 和 PFS 改善相关。
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