吉西他滨，顺铂和杜瓦卢马布对胆道癌患者的免疫化学疗法的功效，安全性和差异结果：多中心现实世界同类
Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort
影响因子:6.70000
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
摘要
由吉西他滨，顺铂和编程的死亡配体组成的免疫化学化学疗法组合的一个抑制剂杜瓦卢马布（GCD）是针对胆道癌症患者（BTC）的新护理标准，该标准是基于Topaz-1研究的积极结果。包括9个德国中心的GCD处理的BTC。回顾性地分析了临床病理基线参数，总生存率（OS），反应率和不良事件（AE）。预后影响是通过Kaplan-Meier分析和Cox回归模型确定的。在2021年至2024年之间，总共165例接受了GCD治疗的患者。中值OS和中值无进展生存期为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％。虽然肝外和肝内BTC的结局相似，但在9个月的胆囊癌（GB-CA）患者中，MOS明显短（95％CI 5.5-12.4； P = 0.02）。在单变量分析≥70岁的单变量分析中，东部合作肿瘤学组（ECOG）绩效状态（PS）≥1，胆囊切除术后状态，GB-CA，GB-CA和高基线CRP值与OS显着相关。在多变量COX回归分析中，ECOGPS≥1和GB-CA仍然是OS的独立预后因素。已有130名患者（78.8％）报告了AE，其中包括149级3-4级AE（25.5％）。一名患者死于严重的感染性肺炎。 17例患者（10.3％）发生了与免疫相关的AE（IR）AE，包括9级3-4级伊拉斯（2.2％），这导致4例患者的治疗中断。在现实生活中，BTC患者的免疫化学疗法是可行的，有效且安全的。我们的结果与3期临床试验结果（TOPAZ-1）相当。 GB-CA患者和/或性能状况降低，需要进一步研究。
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.