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
{"title":"在胆道癌患者中使用吉西他滨、顺铂和德伐卢单抗进行免疫化疗的疗效、安全性和不同结果：多中心真实世界队列。","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23444,"journal":{"name":"United European Gastroenterology Journal","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. 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Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.</p>\",\"PeriodicalId\":23444,\"journal\":{\"name\":\"United European Gastroenterology Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"United European Gastroenterology Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/ueg2.12656\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"United European Gastroenterology Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ueg2.12656","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：根据TOPAZ-1研究的积极结果，由吉西他滨、顺铂和程序性死亡配体1抑制剂durvalumab（GCD）组成的联合免疫化疗是胆道癌（BTC）患者的新治疗标准：我们在德国多中心真实世界患者队列中评估了 GCD 治疗 BTC 的有效性和安全性：方法：纳入德国 9 个中心接受 GCD 治疗的 BTC 患者。对临床病理学基线参数、总生存期（OS）、反应率和不良事件（AEs）进行了回顾性分析。通过卡普兰-梅耶分析和考克斯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名患者。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%。肝外胆管癌和肝内胆管癌的疗效相似，但胆囊癌（GB-CA）患者的生存期明显较短，仅为9个月（95% CI 5.5-12.4；P = 0.02）。在单变量分析中，年龄≥70 岁、东部合作肿瘤学组（ECOG）表现状态（PS）≥1、胆囊切除术后状态、GB-CA 和高基线 CRP 值与 OS 显著相关。在多变量考克斯回归分析中，ECOG PS≥1和GB-CA仍是OS的独立预后因素。130名患者（78.8%）出现了AEs，包括149例3-4级AEs（25.5%）。一名患者死于严重感染性肺炎。17名患者（10.3%）出现了免疫相关（ir）AEs，其中包括9例3-4级irAEs（2.2%），4名患者因此中断了治疗：在现实生活中，对BTC患者进行免疫化疗是可行、有效和安全的。我们的结果与三期临床试验（TOPAZ-1）结果相当。在GB-CA和/或表现状态较差的患者中，疗效有所下降，这值得进一步研究。
Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort.
Background: 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.
Objective: We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
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