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Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

Authors
 Shanu Modi  ;  William Jacot  ;  Toshinari Yamashita  ;  Joohyuk Sohn  ;  Maria Vidal  ;  Eriko Tokunaga  ;  Junji Tsurutani  ;  Naoto T Ueno  ;  Aleix Prat  ;  Yee Soo Chae  ;  Keun Seok Lee  ;  Naoki Niikura  ;  Yeon Hee Park  ;  Binghe Xu  ;  Xiaojia Wang  ;  Miguel Gil-Gil  ;  Wei Li  ;  Jean-Yves Pierga  ;  Seock-Ah Im  ;  Halle C F Moore  ;  Hope S Rugo  ;  Rinat Yerushalmi  ;  Flora Zagouri  ;  Andrea Gombos  ;  Sung-Bae Kim  ;  Qiang Liu  ;  Ting Luo  ;  Cristina Saura  ;  Peter Schmid  ;  Tao Sun  ;  Dhiraj Gambhire  ;  Lotus Yung  ;  Yibin Wang  ;  Jasmeet Singh  ;  Patrik Vitazka  ;  Gerold Meinhardt  ;  Nadia Harbeck  ;  David A Cameron  ;  DESTINY-Breast04 Trial Investigators 
Citation
 NEW ENGLAND JOURNAL OF MEDICINE, Vol.387(1) : 9-20, 2022-07 
Journal Title
NEW ENGLAND JOURNAL OF MEDICINE
ISSN
 0028-4793 
Issue Date
2022-07
MeSH
Antibodies, Monoclonal, Humanized / adverse effects ; Antibodies, Monoclonal, Humanized / therapeutic use ; Antineoplastic Agents, Immunological* / adverse effects ; Antineoplastic Agents, Immunological* / therapeutic use ; Antineoplastic Combined Chemotherapy Protocols / adverse effects ; Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Breast Neoplasms* / drug therapy ; Breast Neoplasms* / genetics ; Breast Neoplasms* / metabolism ; Breast Neoplasms* / secondary ; Camptothecin / analogs & derivatives ; Disease Progression ; Female ; Humans ; Immunoconjugates / adverse effects ; Immunoconjugates / therapeutic use ; Immunohistochemistry ; Receptor, ErbB-2* / analysis ; Receptor, ErbB-2* / biosynthesis ; Receptor, ErbB-2* / genetics ; Trastuzumab* / adverse effects ; Trastuzumab* / therapeutic use
Abstract
Background: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.

Methods: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.

Results: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.

Conclusions: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
Full Text
https://www.nejm.org/doi/10.1056/NEJMoa2203690
DOI
10.1056/NEJMoa2203690
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191707
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