Department of Medicine I, University Medical Center-Campus Lübeck, Lübeck, Germany.
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University Hospital, Magdeburg, Germany.
United European Gastroenterol J. 2024 Nov;12(9):1230-1242. doi: 10.1002/ueg2.12656. Epub 2024 Sep 20.
Combined Immuno-chemotherapy consisting of gemcitabine, cisplatin and the programmed death-ligand one inhibitor durvalumab (GCD) is the new standard of care for patients with biliary tract cancers (BTC) based on positive results of the TOPAZ-1 study.
We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.
Patients with BTC treated with GCD from 9 German centers were included. Clinicopathological baseline parameters, overall survival (OS), response rate and adverse events (AEs) were retrospectively analyzed. The prognostic impact was determined by Kaplan-Meier analyses and Cox regression models.
A total of 165 patients treated with GCD between 2021 and 2024 were included in the study. Median OS and median progression-free survival were 14 months (95% CI 10.3-17.7) and 8 months (95% CI 6.8-9.2), respectively. The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, mOS was significantly shorter in patients with gall bladder cancer (GB-CA) with 9 months (95% CI 5.5-12.4; p = 0.02). In univariate analyses age ≥70 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1, status post cholecystectomy, GB-CA and high baseline CRP values were significantly associated with OS. ECOG PS ≥ 1 and GB-CA remained independent prognostic factors for OS in multivariable cox regression analysis. AEs have been reported in 130 patients (78.8%), including 149 grade 3-4 AEs (25.5%). One patient died of severe infectious pneumonia. Immune-related (ir)AEs occurred in 17 patients (10.3%), including 9 grade 3-4 irAEs (2.2%), which led to treatment interruption in 4 patients.
Immuno-chemotherapy in patients with BTC was feasible, effective and safe in a real-life scenario. Our results were comparable to the phase 3 clinical trial results (TOPAZ-1). Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.
吉西他滨、顺铂和程序性死亡配体 1 抑制剂 durvalumab（GCD）联合免疫化疗是基于 TOPAZ-1 研究阳性结果的胆道癌（BTC）患者的新标准治疗方法。
我们在此评估了 GCD 在德国多中心真实世界患者队列中对 BTC 的疗效和安全性。
纳入了来自 9 家德国中心接受 GCD 治疗的 BTC 患者。回顾性分析了临床病理基线参数、总生存期（OS）、反应率和不良事件（AE）。通过 Kaplan-Meier 分析和 Cox 回归模型确定预后影响。
研究共纳入了 2021 年至 2024 年间接受 GCD 治疗的 165 例患者。中位 OS 和中位无进展生存期分别为 14 个月（95%CI 10.3-17.7）和 8 个月（95%CI 6.8-9.2）。最佳总体反应率为 28.5%，疾病控制率为 65.5%。尽管肝外和肝内 BTC 具有相似的结果，但胆囊癌（GB-CA）患者的 mOS 明显更短，为 9 个月（95%CI 5.5-12.4；p=0.02）。在单因素分析中，年龄≥70 岁、东部合作肿瘤学组（ECOG）表现状态（PS）≥1、胆囊切除术后、GB-CA 和高基线 CRP 值与 OS 显著相关。在多变量 Cox 回归分析中，ECOG PS≥1 和 GB-CA 仍然是 OS 的独立预后因素。130 例患者（78.8%）报告了 AE，包括 149 例 3-4 级 AE（25.5%）。1 例患者死于严重感染性肺炎。免疫相关（ir）AE 发生在 17 例患者（10.3%）中，包括 9 例 3-4 级 irAE（2.2%），其中 4 例患者因 irAE 中断治疗。
在真实环境中，BTC 患者的免疫化疗是可行的、有效和安全的。我们的结果与 3 期临床试验结果（TOPAZ-1）相当。在 GB-CA 患者和/或表现状态降低的患者中，疗效降低，需要进一步研究。
