日本患者HER2阳性晚期胃癌中曲妥珠单抗-德鲁昔单抗的真实世界疗效与安全性（EN-DEAVOR研究）

Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study)

Gastric Cancer

影响因子:5.1

分区:医学2区 / 胃肠肝病学2区肿瘤学2区

发表日期:2025 Jan

作者: Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro,

DOI: 10.1007/s10120-024-01555-w

摘要

基于DESTINY-Gastric01试验结果，日本批准了曲妥珠单抗-德鲁昔单抗（T-DXd）用于HER2阳性晚期胃癌的治疗。本研究旨在收集真实世界数据，评估T-DXd的疗效和安全性。纳入标准包括：≥20岁，组织学确诊为HER2阳性、无法手术切除或复发的晚期或转移性胃癌或胃食管交界处（GEJ）腺癌，且在化疗后病情恶化的患者。主要观察指标包括T-DXd的使用状况、总生存期（OS）、真实世界无进展生存期（rwPFS）、治疗失败时间（TTF）、客观缓解率（ORR）及≥3级不良事件（AEs）的发生频率。分析共纳入312例患者，75.3%为男性，年龄中位数（范围）为70.0（27.0-89.0）岁，ECOG表现状态≥2者占12.2%，腹水患者占43.3%，初始剂量多在5.4-6.4 mg/kg（占78.2%）。中位OS为8.9个月（95% CI：8.0-11.0），rwPFS为4.6个月（95% CI：4.0-5.1），TTF为3.9个月（95% CI：3.4-4.2）。目标病变患者的反应率为42.9%。48.4%的患者出现≥3级AEs，2.6%的患者发生5级AEs，60.9%的患者因AEs调整T-DXd剂量（减药36.9%，中断34.0%，停药23.7%）。未检测到新的安全信号。T-DXd作为三线或更后线治疗在日本临床实践中显示出有效性且安全性可控。UMIN000049032。

Abstract

Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.UMIN000049032.