Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-07-04 DOI:10.1093/oncolo/oyaf148

Lorenzo Antonuzzo, Hidenori Takahashi, Joon Oh Park, Aumkhae Sookprasert, Roopinder Gillmore, Sheng-Shun Yang, Juan Cundom, Mila Petrova, Gina Vaccaro, Marielle Holmblad, Magdalena Żotkiewicz, Julie Wang, Nana Rokutanda, Do-Youn Oh

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引用次数: 0

Abstract

Introduction: We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC).

Methods: Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg/m2] and cisplatin [25 mg/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS).

Results: In durvalumab (n = 338) versus placebo (n = 342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs.

Conclusions: Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis.

Trial registration: ClinicalTrials.gov NCT03875235.

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durvalumab联合吉西他滨和顺铂治疗晚期胆道癌的随机3期TOPAZ-1研究中免疫介导的不良事件

我们在TOPAZ-1 （NCT03875235）研究中评估了durvalumab联合吉西他滨和顺铂（GemCis）治疗晚期胆道癌（aBTC）的免疫介导不良事件（imae）。方法：参与者以1:1的比例随机分为durvalumab （1500 mg）或安慰剂组，静脉滴注加GemCis（吉西他滨[1000 mg/m2]和顺铂[25 mg/m2]）组，然后是durvalumab （1500 mg）或安慰剂Q4W组。我们评估了imAE的发生率、发病时间（TTO）以及与总生存期（OS）的相关性。结果：在durvalumab （n = 338）和安慰剂（n = 342）中，13.9%和4.7%的参与者报告了图像，中位TTO分别为127.0和86.5天。在有影像的受试者中，durvalumab与安慰剂的OS HR为0.59 (95% CI, 0.30-1.23)，而在没有影像的受试者中，durvalumab与安慰剂的OS HR为0.83 （95% CI, 0.70-1.00）。结论：Durvalumab在aBTC中表现出与安慰剂相比的OS获益，无论图像如何，这些图像大多是低级别和可控的。这些亚组的结果与总体初步分析一致。试验注册：ClinicalTrials.gov NCT03875235。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.