Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

N Engl J Med. 2019 Feb 14;380(7):617-628. doi: 10.1056/NEJMoa1814017. Epub 2018 Dec 5.

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 .).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphatic Metastasis
  • Maytansine / adverse effects
  • Maytansine / analogs & derivatives*
  • Maytansine / therapeutic use
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasm, Residual
  • Peripheral Nervous System Diseases / chemically induced
  • Radiotherapy
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / adverse effects
  • Trastuzumab / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • Maytansine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine

Associated data

  • ClinicalTrials.gov/NCT01772472