Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer

Riccardo Masetti, Philip E. Lammers, Magdolna Dank, Richat Abbas, Fiona Hilton, Jennifer Coppola, Ira Jacobs

Risultato della ricerca: Contributo in rivistaArticolo in rivista

26 Citazioni (Scopus)

Abstract

Background: This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (Ctrough) >20 μg/ml at Cycle 5 (Cycle 6 predose). Efficacy endpoints included pathological complete response and objective response rate. Non-inferiority of PF-05280014 to trastuzumab-EU was declared if the lower limit of the 95% confidence interval for the stratified difference between groups in the percentage of patients with Cycle 5 Ctrough >20 μg/ml was above the prespecified non-inferiority margin of – 12.5%. Results: For PF-05280014 vs trastuzumab-EU patients, respectively, 92.1% vs 93.3% had Cycle 5 Ctrough >20 μg/ml; the lower limit of the 95% confidence interval (− 8.02%, 6.49%) for the stratified difference between groups was above the non-inferiority margin (– 12.5%). Pathological complete response (47.0% vs 50.0%) and central radiology review-assessed objective response (88.1% vs 82.0%) rates were comparable. Incidence of all-causality, grade 3–4 treatment-emergent adverse events was 38.1% vs 45.5%; antidrug antibody rates were 0% vs 0.89%. Conclusions: PF-05280014 demonstrated non-inferior pharmacokinetics and comparable efficacy, safety and immunogenicity to trastuzumab-EU in patients with operable HER2-positive breast cancer receiving neoadjuvant chemotherapy.
Lingua originaleEnglish
pagine (da-a)266-273
Numero di pagine8
RivistaBritish Journal of Cancer
Volume119
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized
  • Biosimilar Pharmaceuticals
  • Breast Neoplasms
  • European Union
  • Female
  • Humans
  • Mastectomy
  • Middle Aged
  • Neoadjuvant Therapy
  • Receptor, ErbB-2
  • Trastuzumab
  • Young Adult

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