Durvalumab 加吉西他滨和顺铂治疗晚期胆道癌：全球现实生活中的大量人群。
Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population.
发表日期：2024 Jun 30
作者：
Margherita Rimini, Lorenzo Fornaro, Mario Domenico Rizzato, Lorenzo Antonuzzo, Federico Rossari, Tomoyuki Satake, Hanne Vandeputte, Caterina Vivaldi, Tiziana Pressiani, Jessica Lucchetti, Jin Won Kim, Oluseyi Abidoye, Ilario Giovanni Rapposelli, Stefano Tamberi, Fabian Finkelmeier, Guido Giordano, Federico Nichetti, Hong Jae Chon, Chiara Braconi, Chiara Pirrone, Florian Castet, Emiliano Tamburini, Changhoon Yoo, Alessandro Parisi, Anna Diana, Mario Scartozzi, Gerald W Prager, Antonio Avallone, Marta Schirripa, Il Hwan Kim, Lukas Perkhofer, Ester Oneda, Monica Verrico, Jorge Adeva, Stephen L Chan, Gian Paolo Spinelli, Nicola Personeni, Ingrid Garajova, Maria Grazia Rodriquenz, Silvana Leo, Francesca Salani, Antonio De Rosa, Daniele Lavacchi, Silvia Foti, Masafumi Ikeda, Jeroen Dekervel, Monica Niger, Rita Balsano, Giuseppe Tonini, Minsu Kang, Tanios Bekaii-Saab, Luca Esposito, Alessandra Boccaccino, Vera Himmelsbach, Matteo Landriscina, Selma Ahcene Djaballah, Valentina Zanuso, Gianluca Masi, Sara Lonardi, Lorenza Rimassa, Andrea Casadei-Gardini
来源：
Experimental Hematology & Oncology
摘要：
TOPAZ-1 III 期试验显示，durvalumab 加吉西他滨和顺铂治疗晚期胆道癌 (BTC) 患者具有生存获益。为了了解该组合的真实疗效和耐受性，我们对其一线治疗结果进行了全球多中心回顾性分析。我们纳入了在 39 个地点接受 durvalumab、吉西他滨和顺铂治疗的不可切除、局部晚期或转移性 BTC 患者。 11 个国家（欧洲、美国和亚洲）。主要终点是总生存期 (OS)。共招募了 666 名患者。中位 OS 为 15.1 个月，中位 PFS 为 8.2 个月。研究者评估的总体缓解率为 32.7%，其中 45.2% 的患者病情稳定。高基线 CEA 水平、ECOG PS > 0、转移性疾病和 NLR > 3 与较差的生存率相关。 92.9% 的患者发生了任何级别的不良事件 (AE)（级别 >2：46.6%）。免疫相关 AE (irAE) 的发生率为 20.0%（级别 >2：2.5%）。三例死亡 (0.5%) 被认为与治疗相关，没有与免疫治疗相关。常见的 irAE 包括皮疹（8.2% 所有等级；0.3% 等级 >2）、瘙痒（10.3% 所有等级；0.2% 等级 >2）和甲状腺功能减退症（5.1% 所有等级；0.3% 等级 >2）。因 AE 导致 Durvalumab 停药率为 1.5%。对 ESMO 推荐的基因进行了分析，未发现结果差异。与仅接受化疗的历史队列患者进行的比较分析证实了 durvalumab 与顺铂/吉西他滨联合治疗对生存的积极影响。第一个全球真实世界分析在很大程度上证实了 TOPAZ-1 的研究结果，支持吉西他滨、顺铂和 durvalumab 作为晚期 BTC 患者的一线护理标准。版权所有 © 2024 Elsevier Ltd。保留所有权利。
The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS).666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine.This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.Copyright © 2024 Elsevier Ltd. All rights reserved.