The New England journal of medicine · 2025
Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer.
СтатьяНазвание и аннотация: Перевод в очереди
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Loibl Sibylle, Park Yeon Hee, Shao Zhiming, Huang Chiun-Sheng, Barrios Carlos, Abraham Jame, Prat Aleix, Niikura Naoki, Im Seock-Ah, Li Wei, Li Huiping, Wang Yongsheng, Yao Herui, Kim Sung-Bae, Geng Cui-Zhi, Rodriguez Pantigoso Wuilbert, Ramírez Godinez Francisco Javier, Song Chuangui, Ching Chang Yuan, Antoniazzi Augusto, Chen Shin-Cheh, Li Zhigao, Nowecki Zbigniew, Lim Joline, Mathias Elton, Sato Yuta, Lu Wenjing, Abdel-Monem Hanan, Untch Michael, Geyer Charles E, DESTINY-Breast05 Trial Investigators
Аннотация
BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence.
METHODS: In a phase 3, open-label, international, randomized trial, we investigated postneoadjuvant trastuzumab deruxtecan (T-DXd; 5.4 mg per kilogram of body weight) as compared with trastuzumab emtansine (T-DM1; 3.6 mg per kilogram), the current standard treatment, in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival (including survival free from noninvasive breast cancers and second primary nonbreast cancers). Other end points included overall survival, distant recurrence-free interval, brain metastasis-free interval, and safety.
RESULTS: A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients). At the data-cutoff date, the median duration of follow-up was approximately 30 months in each group. Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001); 3-year invasive disease-free survival was 92.4% and 83.7%, respectively. Invasive-disease events, noninvasive-disease events, or deaths were reported in 52 patients (6.4%) in the T-DXd group and 103 patients (12.6%) in the T-DM1 group (hazard ratio, 0.47; 95% CI, 0.34 to 0.66; P<0.001); 3-year disease-free survival was 92.3% and 83.5%, respectively. The most common adverse events were nausea (71.3% of patients), constipation (32.0%), decreased neutrophil count (31.6%), and vomiting (31.0%) with T-DXd and increased liver-enzyme levels (aspartate aminotransferase [50.2%] and alanine aminotransferase [45.3%]) and decreased platelet count (49.8%) with T-DM1. The incidence of adjudicated drug-related interstitial lung disease was higher with T-DXd than with T-DM1 (9.6% vs. 1.6%). Two patients with interstitial lung disease in the T-DXd group died.
CONCLUSIONS: In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.).
METHODS: In a phase 3, open-label, international, randomized trial, we investigated postneoadjuvant trastuzumab deruxtecan (T-DXd; 5.4 mg per kilogram of body weight) as compared with trastuzumab emtansine (T-DM1; 3.6 mg per kilogram), the current standard treatment, in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival (including survival free from noninvasive breast cancers and second primary nonbreast cancers). Other end points included overall survival, distant recurrence-free interval, brain metastasis-free interval, and safety.
RESULTS: A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients). At the data-cutoff date, the median duration of follow-up was approximately 30 months in each group. Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001); 3-year invasive disease-free survival was 92.4% and 83.7%, respectively. Invasive-disease events, noninvasive-disease events, or deaths were reported in 52 patients (6.4%) in the T-DXd group and 103 patients (12.6%) in the T-DM1 group (hazard ratio, 0.47; 95% CI, 0.34 to 0.66; P<0.001); 3-year disease-free survival was 92.3% and 83.5%, respectively. The most common adverse events were nausea (71.3% of patients), constipation (32.0%), decreased neutrophil count (31.6%), and vomiting (31.0%) with T-DXd and increased liver-enzyme levels (aspartate aminotransferase [50.2%] and alanine aminotransferase [45.3%]) and decreased platelet count (49.8%) with T-DM1. The incidence of adjudicated drug-related interstitial lung disease was higher with T-DXd than with T-DM1 (9.6% vs. 1.6%). Two patients with interstitial lung disease in the T-DXd group died.
CONCLUSIONS: In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.).