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N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017. [Epub ahead of print]

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.

Author information

1
From the German Breast Group, Neu-Isenburg (G.M., S.L., H.H.F., P.W.), the Center for Hematology and Oncology Bethanien, Frankfurt (S.L.), the AGO-B and HELIOS Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), the Arbeitsgemeinschaft Gynäkologische Onkologie - Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), and Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg (P.W.) - all in Germany; the National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation and Orlando Health University of Florida Health Cancer Center, Orlando (E.P.M.); the NSABP Foundation and Allegheny Health Network Cancer Institute (N.W.) and the NSABP Foundation and University of Pittsburgh Cancer Institute, School of Medicine (P.R.), Pittsburgh; Hospital Universitario La Paz-Instituto de Investigación Hospital Universitario La Paz, Madrid (A.R.); Institut Régional du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier, France (W.J.); the NSABP Foundation and Providence Portland Medical Center, Portland, OR (A.K.C.); the National Cancer Institute, Mexico City (C.A.-S.); the NSABP Foundation and Stanford University School of Medicine, Stanford (I.L.W.), and Genentech, South San Francisco (L.H.L., D.T., M.S., S.M.S.) - both in California; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the Ireland Cooperative Oncology Research Group, Dublin (J.P.C.); Fudan University Shanghai Cancer Center (Z.S.) and Roche (China) Holding (H.W.), Shanghai; the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy (E.R.C.); F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom (H.D.); and the NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond (C.E.G.).

Abstract

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<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.

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 .).

PMID:
30516102
DOI:
10.1056/NEJMoa1814017

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