吉西他滨、顺铂与达瓦卢单抗免疫-化疗在胆道癌患者中的疗效、安全性及差异性结局：多中心真实世界队列研究

Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort

United European Gastroenterology Journal

影响因子:6.7

分区:医学2区 / 胃肠肝病学3区

发表日期:2024 Nov

作者: Katharina Mitzlaff, Martha M Kirstein, Christian Müller, Marino Venerito, Alexander Olkus, Michael T Dill, Arndt Weinmann, Lorenz Kocheise, Alina Busch, Kornelius Schulze, Gabriel Allo, Dirk-Thomas Waldschmidt, Maryam Barsch, Bertram Bengsch, Michael Quante, Maria A Gonzalez-Carmona, Vera Himmelsbach, Fabian Finkelmeier, Roman Kloeckner, Peter Schirmacher, Jens U Marquardt, Carolin Zimpel

DOI: 10.1002/ueg2.12656

摘要

基于TOPAZ-1研究的积极结果，联合免疫-化疗方案（吉西他滨、顺铂和程序性死亡配体-1抑制剂达瓦卢单抗（GCD））已成为胆道癌（BTC）患者的新的治疗标准。本研究在德国多中心真实世界队列中评估了GCD治疗BTC的疗效和安全性。纳入了来自9个德国中心的接受GCD治疗的患者。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（AEs）。采用Kaplan-Meier分析和Cox回归模型确定预后影响因素。共纳入2021至2024年间接受GCD治疗的165例患者。中位OS为14个月（95% CI 10.3-17.7），中位无进展生存期（PFS）为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%。虽然肝外和肝内胆道癌的结果相似，胆囊癌（GB-CA）患者的中位OS显著更短，为9个月（95% CI 5.5-12.4；p=0.02）。单变量分析显示，年龄≥70岁、Eastern Cooperative Oncology Group（ECOG）性能状态（PS）≥1、胆囊切除术史、GB-CA和高基线CRP值与OS显著相关。多变量Cox回归分析中，ECOG PS≥1和GB-CA仍是独立的预后因素。130名患者（78.8%）出现不良事件，其中149例为3-4级AEs（25.5%），一例患者死于严重感染性肺炎。17名患者（10.3%）出现免疫相关不良事件（irAEs），其中9例为3-4级（2.2%），4例因irAEs中断治疗。胆道癌患者的免疫-化疗在实际临床中是可行的、有效的且安全的。我们的结果与三期临床试验（TOPAZ-1）相当。在GB-CA和/或性能状态较差的患者中观察到疗效降低，需进一步研究。

Abstract

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.