title: Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy.
  
  
  METHODS
  Patients with measurable HER2(+) metastatic breast cancer, < or = 3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) > or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v. followed by 6 mg/kg trastuzumab and 420 mg pertuzumab every 3 weeks. Cardiac evaluation and tumor response were assessed every 3 and 6 weeks, respectively.
  
  
  RESULTS
  Eleven patients received 64 cycles of trastuzumab plus pertuzumab. A total of 92 echocardiograms and 8 cardiac magnetic resonance imaging studies were done. With the lower limit of normal LVEF 55%, left ventricular systolic dysfunction was observed in six patients, three grade 1, two grade 2, and one grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The objective response rate was 18%. Two patients had partial responses, three had stable disease, and six had progressive disease. The median time to progression was 6 weeks. In baseline tumors from formalin-fixed paraffin-embedded primary and/or metastatic tumor biopsies, pHER2-Y1248 trended toward an increase in patients with partial response compared with those with stable disease/progressive disease (P = 0.095).
  
  
  CONCLUSIONS
  Trastuzumab plus pertuzumab may have clinical benefit in selected patients who have previously been treated with trastuzumab. Cardiac toxicity, although asymptomatic in most cases, was associated with this treatment. Further evaluation of efficacy of this combination is required to define the overall risks and benefits.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Chia C
authors.initials: CC
authors.lastname: Portera
authors.forename: Janice M
authors.initials: JM
authors.lastname: Walshe
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Rosing
authors.forename: Neelima
authors.initials: N
authors.lastname: Denduluri
authors.forename: Arlene W
authors.initials: AW
authors.lastname: Berman
authors.forename: Ujala
authors.initials: U
authors.lastname: Vatas
authors.forename: Margarita
authors.initials: M
authors.lastname: Velarde
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chow
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Diana
authors.initials: D
authors.lastname: Nguyen
authors.forename: Sherry X
authors.initials: SX
authors.lastname: Yang
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab