Kawakami Hisato, Nakanishi Koki, Makiyama Akitaka, Konishi Hirotaka, Morita Satoshi, Narita Yukiya, Sugimoto Naotoshi, Minashi Keiko, Imano Motohiro, Inamoto Rin, Kodera Yasuhiro, Kume Hiroki, Yamaguchi Keita, Hashimoto Wataru, Muro Kei
Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Japan.
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Gastric Cancer. 2025 Jan;28(1):51-61. doi: 10.1007/s10120-024-01555-w. Epub 2024 Oct 10.
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.
基于DESTINY-Gastric01试验的结果，曲妥珠单抗-德曲妥珠单抗（T-DXd）在日本被批准用于治疗HER2阳性晚期胃癌患者。本研究旨在收集真实世界数据，并评估T-DXd的有效性和安全性。
本回顾性队列研究纳入了在开始使用T-DXd治疗时年龄≥20岁、经组织病理学确诊为HER2阳性不可切除的晚期或复发性胃癌或胃食管交界（GEJ）腺癌且化疗后病情进展的患者。主要结局包括T-DXd治疗状态、总生存期（OS）、真实世界无进展生存期（rwPFS）、治疗失败时间（TTF）、客观缓解率以及≥3级不良事件（AE）的发生率。
纳入分析的312例患者中，75.3%为男性，中位（范围）年龄为70.0（27.0 - 89.0）岁，12.2%的患者东部肿瘤协作组（ECOG）体能状态评分≥2，43.3%的患者有腹水，78.2%的患者初始T-DXd剂量>5.4 - ≤6.4mg/kg。中位（95%置信区间）OS、rwPFS和TTF（月）分别为8.9（8.0 - 11.0）、4.6（4.0 - 5.1）和3.9（3.4 - 4.2）。有靶病灶患者的缓解率为42.9%。共有48.4%的患者发生≥3级AE，2.6%的患者发生5级AE，60.9%的患者发生导致T-DXd剂量调整的AE（减量：36.9%，中断：34.0%或停药：23.7%）。未检测到新的安全信号。
在日本临床实践中，T-DXd作为HER2阳性胃癌或GEJ癌患者的三线或更后线治疗有效且安全性可控。
UMIN000049032。
