Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer
Mené sur 226 patientes atteintes d'un cancer du sein HER2+ opérable, cet essai randomisé compare les caractéristiques pharmacocinétiques, l'efficacité, du point de vue du taux de réponse pathologique complète et du taux de réponse objective, et la toxicité d'un composé appelé PF-05280014, un biosimilaire du trastuzumab, et le trastuzumab, en traitement néoadjuvant
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.
British Journal of Cancer , article en libre accès, 2018