Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.
The New England journal of medicine
BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.
METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).
RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P
CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).
Women & Children
von Minckwitz, Gunter; Huang, Chiun-Sheng; Mano, Max S; Loibl, Sibylle; Mamounas, Eleftherios P; Untch, Michael; Wolmark, Norman; Rastogi, Priya; Schneeweiss, Andreas; Redondo, Andres; Fischer, Hans H; Jacot, William; Conlin, Alison; Arce-Salinas, Claudia; Wapnir, Irene L; Jackisch, Christian; DiGiovanna, Michael P; Fasching, Peter A; Crown, John P; Wülfing, Pia; Shao, Zhimin; Rota Caremoli, Elena; Wu, Haiyan; Lam, Lisa H; Tesarowski, David; Smitt, Melanie; Douthwaite, Hannah; Singel, Stina M; and Geyer, Charles E, "Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer." (2018). Articles, Abstracts, and Reports. 999.