trastuzumab emtansine (n=743) vs. trastuzumab (n=743)
randomized controlled trial
trastuzumab emtasine (T-DM1)
T-DM1: 3.6 mg per kg of body weight IV every 3 weeks for 14 cycles
trastuzumab
trastuzumab: 6 mg per kg IV every 3 weeks for 14 cycles (a loading dose of 8 mg of trastuzumab per kg was administered if more than 6 weeks had relapsed since the preceding dose of trastuzumab)
Patients who discontinued T-DM1 early because of toxic effects could complete 14 cycles of trial treatment with trastuzumab at the discretion of the investigator.
es-BC - HER2 positive - (neo)adjuvant (NA)
Exclusion criteria: gross residual disease remaining after mastectomy or positive margins after breast-conserving surgery; progressive disease during neoadjuvant therapy; and cardiopulmonary dysfunction (heart failure NYHA class II or higher; or a history of a reduction in the left ventricular ejection fraction to less than 40% with previous therapy).
open-label
273 trial sites in 28 countries
P3 / hierarchical test, 5% (2-sided): IDFS > OS / 1 IA of IDFS (p value<0.0124 / final IDFS: p<0.0462) and 3 IA of OS (IA1: p<0.0009 / IA 2: p<0.0053 / AI 3: p<0.0184 / final OS: p<0.0435).
trastuzumab emtasine improves IDFS compare to trastuzumab to patients with non-metastatic HER2-positive BC
Harbeck (TDM-1), 2017
trastuzumab emtansine (n=119) vs. trastuzumab plus endocrine therapy (n=129)
randomized controlled trial
trastuzumab emtasine
trastuzumab emtasine: 3.6mg/kg every 3weeks for 4 cycles
trastuzumab plus endocrine therapy
trastuzumab: at a loading dose of 8 mg/kg and then 6 mg/kg every 3 weeks for 3 more cycles / endorine therapy: tamoxifen in premenopausal women and aromatase inhibitors in postmenopausal women
Gonadotropin-releasing hormone analogs were allowed in premenopausal patients
es-BC - HER2 positive - (neo)adjuvant (NA)
Exclusion criteria: nonoperable and inflammatory BC
open label
48 centers
P2 / 2 one-sided tests or proportions (arm A v arm C and arm B v armC) were planned at an a of .025 under the assumption of at least 25% pCRin both T-DM1 arms (arms A and, B), compared with a 10% pCR rate in the trastuzumab arm (arm C)