曲妥珠单抗德曲妥珠单抗用于中国既往接受过治疗的人表皮生长因子受体2阳性局部晚期/转移性胃或胃食管交界腺癌患者（DESTINY-Gastric06）：一项单臂、多中心、2期试验的结果
Trastuzumab deruxtecan in patients from China with previously treated human epidermal growth factor receptor 2-positive locally advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (DESTINY-Gastric06): results from a single-arm, multicenter, phase 2 trial.
作者信息
Peng Zhi, Chen Ping, Lu Jin, Wan Yiye, Zheng Yulong, Ye Feng, Yang Jianwei, Liu Ying, Pan Hongming, Sun Meili, Fan Qingxia, Yuan Ying, Chen Kai, Sun Zhuoer, Tian Han, Xia Ye, Shen Lin
机构信息
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of GI Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
General Hospital of Ningxia Medical University, 692 Shengli St, Xingqing Qu, Yinchuan Shi Ningxia Huizuzizhiqu, Yinchuan, Ningxia, 750000, China.
出版信息
EClinicalMedicine. 2025 Aug 11;87:103404. doi: 10.1016/j.eclinm.2025.103404. eCollection 2025 Sep.
BACKGROUND
Trastuzumab deruxtecan (T-DXd; 6·4 mg/kg) is approved for metastatic human epidermal growth factor receptor 2 (HER2)-positive (HER2+) gastric or gastroesophageal junction (GEJ) adenocarcinoma after a trastuzumab-based regimen. We report the final analysis of DESTINY-Gastric06, evaluating T-DXd in pretreated patients from China with advanced HER2+ gastric cancers (GC).
METHODS
The single-arm, multicenter, phase 2 DESTINY-Gastric06 trial (NCT04989816) enrolled patients from China with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+; locally documented) advanced gastric or GEJ adenocarcinoma with two or more prior treatments. Patients received T-DXd 6·4 mg/kg intravenous infusion every 3 weeks. The primary endpoint was confirmed objective response rate in HER2+ (IHC 3+ or IHC 2+/in situ hybridization-positive) tumors (full analysis set) by independent central review. Secondary endpoints included investigator-assessed confirmed objective response rate, progression-free survival by independent central review, overall survival, and safety.
FINDINGS
Of 126 patients screened between August 20, 2021, and December 7, 2022, 95 were enrolled (intent-to-treat; 73 patients had centrally confirmed HER2+ tumors). Median follow up was 10·2 months. Among the 73 patients, confirmed objective response rate (95% confidence interval) by independent central review was 28·8% (18·8-40·6%) and by investigator assessment was 37·0% (26·0-49·1%). Median progression-free survival by independent central review was 5·7 months. Median overall survival was 11·1 months. The most common Grade 1-2 adverse event was white blood cell count decreased (53·7%; 51/95).
INTERPRETATION
Consistent with other GC trials, T-DXd showed durable benefit, with no new safety signals, in pretreated patients from China with HER2+ advanced GC; data support T-DXd as a third- or later-line therapeutic option in this population.
FUNDING
AstraZeneca.
背景
曲妥珠单抗德鲁昔单抗（T-DXd；6.4mg/kg）已被批准用于在基于曲妥珠单抗的治疗方案后治疗转移性人表皮生长因子受体2（HER2）阳性（HER2+）胃癌或胃食管交界（GEJ）腺癌。我们报告了DESTINY-Gastric06的最终分析结果，评估了T-DXd在来自中国的既往接受过治疗的晚期HER2+胃癌（GC）患者中的疗效。
方法
单臂、多中心、2期DESTINY-Gastric06试验（NCT04989816）纳入了来自中国的HER2+（免疫组织化学[IHC]3+或IHC 2+；当地记录）晚期胃癌或GEJ腺癌且接受过两种或更多种既往治疗的患者。患者每3周接受一次6.4mg/kg的T-DXd静脉输注。主要终点是通过独立中央审查确定的HER2+（IHC 3+或IHC 2+/原位杂交阳性）肿瘤（全分析集）的确认客观缓解率。次要终点包括研究者评估的确认客观缓解率、独立中央审查评估的无进展生存期、总生存期和安全性。
结果
在2021年8月20日至2022年12月7日期间筛选的126例患者中，95例患者入组（意向性分析集；73例患者经中心确认HER2+肿瘤）。中位随访时间为10.2个月。在这73例患者中，独立中央审查确定的确认客观缓解率（95%置信区间）为28.8%（18.8-40.6%），研究者评估的确认客观缓解率为37.0%（26.0-49.1%）。独立中央审查评估的中位无进展生存期为5.7个月。中位总生存期为11.1个月。最常见的1-2级不良事件是白细胞计数降低（53.7%；51/95）。
解读
与其他GC试验一致，T-DXd在来自中国的既往接受过治疗的HER2+晚期GC患者中显示出持久疗效，且无新的安全信号；数据支持T-DXd作为该人群的三线或更后线治疗选择。
资助
阿斯利康。
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