Shanu Modi, William Jacot, Hiroji Iwata, Yeon Hee Park, Maria Vidal Losada, Wei Li, Junji Tsurutani, Naoto T Ueno, Khalil Zaman, Aleix Prat, Konstantinos Papazisis, Hope S Rugo, Toshinari Yamashita, Nadia Harbeck, Seock-Ah Im, Michelino De Laurentiis, Jean-Yves Pierga, Xiaojia Wang, Andrea Gombos, Eriko Tokunaga, Cecilia Orbegoso Aguilar, Lotus Yung, Feng Xiao, Yingkai Cheng, David Cameron
{"title":"曲妥珠单抗德鲁司替康治疗her2低转移性乳腺癌:随机3期DESTINY-Breast04试验的长期生存分析","authors":"Shanu Modi, William Jacot, Hiroji Iwata, Yeon Hee Park, Maria Vidal Losada, Wei Li, Junji Tsurutani, Naoto T Ueno, Khalil Zaman, Aleix Prat, Konstantinos Papazisis, Hope S Rugo, Toshinari Yamashita, Nadia Harbeck, Seock-Ah Im, Michelino De Laurentiis, Jean-Yves Pierga, Xiaojia Wang, Andrea Gombos, Eriko Tokunaga, Cecilia Orbegoso Aguilar, Lotus Yung, Feng Xiao, Yingkai Cheng, David Cameron","doi":"10.1038/s41591-025-03981-4","DOIUrl":null,"url":null,"abstract":"<p><p>In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 .</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0000,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial.\",\"authors\":\"Shanu Modi, William Jacot, Hiroji Iwata, Yeon Hee Park, Maria Vidal Losada, Wei Li, Junji Tsurutani, Naoto T Ueno, Khalil Zaman, Aleix Prat, Konstantinos Papazisis, Hope S Rugo, Toshinari Yamashita, Nadia Harbeck, Seock-Ah Im, Michelino De Laurentiis, Jean-Yves Pierga, Xiaojia Wang, Andrea Gombos, Eriko Tokunaga, Cecilia Orbegoso Aguilar, Lotus Yung, Feng Xiao, Yingkai Cheng, David Cameron\",\"doi\":\"10.1038/s41591-025-03981-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 .</p>\",\"PeriodicalId\":19037,\"journal\":{\"name\":\"Nature Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":50.0000,\"publicationDate\":\"2025-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41591-025-03981-4\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41591-025-03981-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial.
In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 .
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