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)

Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22.

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.

Patients and 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.

Conclusion: The combination of P with H and standard chemotherapy resulted in low rates of symptomatic LVSD.

Trial registration: ClinicalTrials.gov NCT00976989.

Keywords: HER2; LVSD; early breast cancer; neoadjuvant; pertuzumab; trastuzumab.

Publication types

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

MeSH terms

  • Anthracyclines / adverse effects
  • Anthracyclines / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Docetaxel
  • Epirubicin / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Heart / drug effects
  • Humans
  • Inflammatory Breast Neoplasms / drug therapy*
  • Inflammatory Breast Neoplasms / surgery
  • Neoadjuvant Therapy / methods*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Stroke Volume / drug effects
  • Taxoids / therapeutic use
  • Trastuzumab
  • Ventricular Function, Left / drug effects*

Substances

  • Anthracyclines
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • Carboplatin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • pertuzumab
  • Trastuzumab
  • Fluorouracil

Supplementary concepts

  • FEC protocol

Associated data

  • ClinicalTrials.gov/NCT00976989