title: Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  Women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) can respond to multiple lines of anti-HER2 therapy. It is unknown whether these patients will derive further clinical benefit following treatment with trastuzumab-MCC-DM1 (T-DM1).
  
  
  METHODS
  We retrospectively identified HER2-positive MBC patients treated with T-DM1 and characterized outcomes during subsequent lines of anti-HER2 therapy. Response was determined by a blinded radiology review. Time-dependent analyses were carried out using Kaplan-Meier estimates.
  
  
  RESULTS
  We identified 23 patients treated with single-agent T-DM1 and report on the 20 patients who discontinued protocol therapy. All patients received trastuzumab-based metastatic therapy before initiation of T-DM1 [median 7 regimens (range 3-14)]. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after discontinuing T-DM1. Partial response to either first- or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib. Median durations of therapy to first- and second-subsequent regimens after T-DM1 were 5.5 and 6.4 months, respectively.
  
  
  CONCLUSIONS
  In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab- and/or lapatinib-based regimens.
authors.affiliation: Departments of Medical Oncology.
authors.forename: E M
authors.initials: EM
authors.lastname: Olson
authors.affiliation: Departments of Medical Oncology.
authors.forename: N U
authors.initials: NU
authors.lastname: Lin
authors.affiliation: Departments of Radiology.
authors.forename: P J
authors.initials: PJ
authors.lastname: DiPiro
authors.affiliation: Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Najita
authors.affiliation: Departments of Medical Oncology.
authors.forename: I E
authors.initials: IE
authors.lastname: Krop
authors.affiliation: Departments of Medical Oncology.
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Departments of Medical Oncology. Electronic address: hburstein@partners.org.
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008453:Maytansine / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage; D012189:Retrospective Studies; D000068878:Trastuzumab; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine