title: Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).
abstract: BACKGROUND
  Pertuzumab (P) combined with trastuzumab (H)-based chemotherapy improves efficacy in early and advanced HER2-positive breast cancer. We assessed the tolerability, with particular focus on cardiac safety, of H and P with chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.
  
  
  METHODS
  In this multicenter, open-label phase II study, patients with operable, locally advanced, or inflammatory breast cancer were randomized 1 : 1 : 1 to receive six neoadjuvant cycles q3w (Arm A: 5-fluorouracil, epirubicin, cyclophosphamide [FEC] + H + P ×3 → docetaxel [T] + H + P ×3; Arm B: FEC ×3 → T + H + P ×3; Arm C: T + carboplatin + H [TCH]+P ×6). pCR was assessed at surgery and adjuvant therapy given to complete 1 year of H.
  
  
  RESULTS
  Two hundred twenty-five patients were randomized. During neoadjuvant treatment, two patients (2.7%; Arm B) experienced symptomatic left ventricular systolic dysfunction (LVSD) and 11 patients (Arm A: 4 [5.6%]; Arm B: 4 [5.3%]; Arm C: 3 [3.9%]) had declines in left ventricular ejection fraction of ≥10% points from baseline to <50%. Diarrhea was the most common adverse event. pCR (ypT0/is) was reported for 61.6% (Arm A), 57.3% (Arm B), and 66.2% (Arm C) of patients.
  
  
  CONCLUSIONS
  The combination of P with H and standard chemotherapy resulted in low rates of symptomatic LVSD.
authors.affiliation: National Center for Tumor Diseases, University Hospital, Heidelberg, Germany. schneeweiss@med.uni-heidelberg.de
authors.forename: A
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: S
authors.initials: S
authors.lastname: Chia
authors.forename: T
authors.initials: T
authors.lastname: Hickish
authors.forename: V
authors.initials: V
authors.lastname: Harvey
authors.forename: A
authors.initials: A
authors.lastname: Eniu
authors.forename: R
authors.initials: R
authors.lastname: Hegg
authors.forename: C
authors.initials: C
authors.lastname: Tausch
authors.forename: J H
authors.initials: JH
authors.lastname: Seo
authors.forename: Y-F
authors.initials: YF
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Ratnayake
authors.forename: V
authors.initials: V
authors.lastname: McNally
authors.forename: G
authors.initials: G
authors.lastname: Ross
authors.forename: J
authors.initials: J
authors.lastname: Cortés
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D020360:Neoadjuvant Therapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016190:Carboplatin; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: HER2; LVSD; early breast cancer; neoadjuvant; pertuzumab; trastuzumab