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 trialResearch in context

Summary: 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,...

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Main Authors: Zhi Peng, Ping Chen, Jin Lu, Yiye Wan, Yulong Zheng, Feng Ye, Jianwei Yang, Ying Liu, Hongming Pan, Meili Sun, Qingxia Fan, Ying Yuan, Kai Chen, Zhuoer Sun, Han Tian, Ye Xia, Lin Shen
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:EClinicalMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589537025003360
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Summary:Summary: 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.
ISSN:2589-5370