Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

Modi, Shanu; Jacot, William; Yamashita, Toshinari; Sohn, Joohyuk; Vidal, Maria; Tokunaga, Eriko; Tsurutani, Junji; Ueno, Naoto T.; Prat, Aleix; Chae, Yee Soo; Lee, Keun Seok; Niikura, Naoki; Park, Yeon Hee; Xu, Binghe; Wang, Xiaojia; Gil-Gil, Miguel; Li, Wei; Pierga, Jean-Yves; Im, Seock-Ah; Moore, Halle C. F.; Rugo, Hope S.; Yerushalmi, Rinat; Zagouri, Flora; Gombos, Andrea; Kim, Sung-Bae; Liu, Qiang; Luo, Ting; Saura, Cristina; Schmid, Peter; Sun, Tao; Gambhire, Dhiraj; Yung, Lotus; Wang, Yibin; Singh, Jasmeet; Vitazka, Patrik; Meinhardt, Gerold; Harbeck, Nadia und Cameron, David A. (2022): Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. In: New England Journal of Medicine, Bd. 387, Nr. 1: S. 9-20

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, .)

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0028-4793
• Sprache: Englisch