TY - JOUR
T1 - Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
AU - Modi, Shanu
AU - Jacot, William
AU - Yamashita, Toshinari
AU - Sohn, Joohyuk
AU - Vidal, Maria
AU - Tokunaga, Eriko
AU - Tsurutani, Junji
AU - Ueno, Naoto T.
AU - Prat, Aleix
AU - Chae, Yee Soo
AU - Lee, Keun Seok
AU - Niikura, Naoki
AU - Park, Yeon Hee
AU - Xu, Binghe
AU - Wang, Xiaojia
AU - Gil-Gil, Miguel
AU - Li, Wei
AU - Pierga, Jean Yves
AU - Im, Seock Ah
AU - Moore, Halle C.F.
AU - Rugo, Hope S.
AU - Yerushalmi, Rinat
AU - Zagouri, Flora
AU - Gombos, Andrea
AU - Kim, Sung Bae
AU - Liu, Qiang
AU - Luo, Ting
AU - Saura, Cristina
AU - Schmid, Peter
AU - Sun, Tao
AU - Gambhire, Dhiraj
AU - Yung, Lotus
AU - Wang, Yibin
AU - Singh, Jasmeet
AU - Vitazka, Patrik
AU - Meinhardt, Gerold
AU - Harbeck, Nadia
AU - Cameron, David A.
N1 - Publisher Copyright:
© 2022 Massachusetts Medical Society.
PY - 2022/7/7
Y1 - 2022/7/7
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa2203690
DO - 10.1056/NEJMoa2203690
M3 - Article
C2 - 35665782
AN - SCOPUS:85133263146
SN - 0028-4793
VL - 387
SP - 9
EP - 20
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 1
ER -