title: Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study.
abstract: BACKGROUND
  We report cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel observed in the phase III study CLEOPATRA in patients with HER2-positive first-line metastatic breast cancer (MBC).
  
  
  METHODS
  Left ventricular ejection fraction (LVEF) ≥ 50% and ECOG performance status of 0 or 1 were required for study entry. During the study, LVEF assessments took place every 9 weeks. Pertuzumab/placebo was given at 840 mg, then 420 mg q3w; trastuzumab was administered at 8 mg/kg, then 6 mg/kg q3w, and docetaxel was initiated at 75 mg/m(2) q3w.
  
  
  RESULTS
  The incidence of cardiac adverse events (all grades) was 16.4% in the placebo arm and 14.5% in the pertuzumab arm, with left ventricular systolic dysfunction (LVSD, all grades) being the most frequently reported event (8.3% versus 4.4% in the placebo and pertuzumab arm). Declines in LVEF by ≥ 10% points from baseline and to <50% were reported in 6.6% and 3.8% of patients in the placebo and pertuzumab arm, respectively. Seventy-two percent (placebo arm) and 86.7% (pertuzumab arm) of those patients recovered to a value ≥ 50%. The incidence of symptomatic LVSD was low, occurring in 1.8% (n = 7) versus 1.0% (n = 4) of patients in the placebo and pertuzumab arm. In 8/11 patients, the symptomatic LVSD had resolved at data cutoff.
  
  
  CONCLUSIONS
  The combination of pertuzumab plus trastuzumab plus docetaxel did not increase the incidence of cardiac adverse events, including LVSD, compared with the control arm in HER2-positive MBC. The majority of cardiac adverse events were reversible.
authors.affiliation: Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC 20010, USA. Sandra.M.Swain@MedStar.net
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ewer
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.forename: Adam
authors.initials: A
authors.lastname: Knott
authors.forename: Emma
authors.initials: E
authors.lastname: Clark
authors.forename: Mark C
authors.initials: MC
authors.lastname: Benyunes
authors.forename: Graham
authors.initials: G
authors.lastname: Ross
authors.forename: José
authors.initials: J
authors.lastname: Baselga
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D013318:Stroke Volume / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C485206:pertuzumab