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,...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537025003360 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849404846176731136 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Zhi Peng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7eb9c79a603342e5a71edc428dc0b1d8 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-7eb9c79a603342e5a71edc428dc0b1d82025-08-20T03:36:49ZengElsevierEClinicalMedicine2589-53702025-09-018710340410.1016/j.eclinm.2025.103404Trastuzumab 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 contextZhi Peng0Ping Chen1Jin Lu2Yiye Wan3Yulong Zheng4Feng Ye5Jianwei Yang6Ying Liu7Hongming Pan8Meili Sun9Qingxia Fan10Ying Yuan11Kai Chen12Zhuoer Sun13Han Tian14Ye Xia15Lin Shen16State 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; Corresponding author. 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, ChinaSichuan Cancer Hospital, 55 Renmin South Road, Section 4, Wuhou District, Chengdu, Sichuan, 610044, ChinaJiangxi Cancer Hospital, 519 East Beijing Road, 36, Nanchang, Jiangxi, 330029, ChinaThe First Affiliated Hospital Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, ChinaThe First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Siming District, Xiamen, 361003, ChinaFujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian Province, 350014, ChinaHenan Cancer Hospital, 127 Dongming Road, Jinshui District, Zhengzhou, Henan, ChinaSir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310016, ChinaJinan Central Hospital, 105 Jiefang Road, Lixia District, Jinan, Shandong, 250013, ChinaThe First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 45005, ChinaDepartment of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jie Fang Rd, Shangcheng District, Hangzhou, Zhejiang, 310009, ChinaThe First Affiliated Hospital of Soochow University, 296 Shizi St, Cang Lang Qu, Suzhou, Jiangsu, 215005, ChinaOncology, Oncology R&D, AstraZeneca, No. 88, North Xizang Road, Jing'An District, Shanghai, 200071, ChinaOncology, Oncology R&D, AstraZeneca, No. 88, North Xizang Road, Jing'An District, Shanghai, 200071, ChinaOncology, Oncology R&D, AstraZeneca, No. 88, North Xizang Road, Jing'An District, Shanghai, 200071, ChinaState 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; Corresponding author: Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.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.http://www.sciencedirect.com/science/article/pii/S2589537025003360HER2+T-DXdGastric cancerGastroesophageal junction adenocarcinoma |
| spellingShingle | 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 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 EClinicalMedicine HER2+ T-DXd Gastric cancer Gastroesophageal junction adenocarcinoma |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | HER2+ T-DXd Gastric cancer Gastroesophageal junction adenocarcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025003360 |
| work_keys_str_mv | AT zhipeng trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT pingchen trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT jinlu trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT yiyewan trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT yulongzheng trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT fengye trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT jianweiyang trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT yingliu trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT hongmingpan trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT meilisun trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT qingxiafan trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT yingyuan trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT kaichen trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT zhuoersun trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT hantian trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT yexia trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext AT linshen trastuzumabderuxtecaninpatientsfromchinawithpreviouslytreatedhumanepidermalgrowthfactorreceptor2positivelocallyadvancedmetastaticgastricorgastroesophagealjunctionadenocarcinomadestinygastric06resultsfromasinglearmmulticenterphase2trialresearchincontext |