407TiP - Treatment of Patients with Hormone Receptor (HR)-Positive and HER2-Positive Locally Advanced or Metastatic BC with a Combination of Pertuzumab and Trastuzumab Plus an Aromatase Inhibitor (AI): an Open-Label Randomised Phase II Study (Pertain)

Abstract

ABSTRACT Background Development of resistance to endocrine therapy in patients (pts) with breast cancer (BC) is a major clinical concern. Preclinical studies suggest that blockade of HR with HER2 inhibition may be key to overcoming resistance and improving clinical outcomes. The combination of pertuzumab (P) and trastuzumab (H) with docetaxel significantly improves outcomes by a comprehensive blockade of HER2 signalling. However, initial results suggest that this benefit may be less apparent in HR-positive pts. PERTAIN is the first study to assess whether a fuller blockade of HER signalling with P and H in conjunction with an AI may resensitise HER2-positive tumours to endocrine therapy and provide an effective first-line treatment option in pts with HR-positive and HER2-positive advanced BC. Methods PERTAIN is a multicentre, open-label, Phase II trial for postmenopausal women with HER2-positive and HR-positive locally advanced/metastatic BC to assess the efficacy of P plus H with an AI as first-line therapy. Pts will be randomised 1:1 to Arm 1 (P: 840 mg initial dose, 420 mg q3w iv; H: 8 mg/kg initial dose, 6 mg/kg q3w iv; AI [anastrozole 1 mg or letrozole 2.5 mg qd po]) or Arm 2 (H + AI at same dose as Arm 1). Induction chemotherapy (CT) (docetaxel or paclitaxel) may be given to pts for up to 18 weeks at the investigator's discretion. Administration of study medications will continue until disease progression or unacceptable toxicity. Pts must not have been treated with anti-HER2 agents, except H and/or lapatinib in the (neo)adjuvant setting, and must have no CNS involvement or clinically significant cardiovascular disease. The primary endpoint is progression free survival (PFS); secondary endpoints include overall survival, overall response rate, clinical benefit rate, duration of response, time to response, safety and tolerability, and QoL. The study opened in April 2012 and will recruit 250 pts. The main analysis for the primary endpoint (after 165 PFS events) will include a treatment group variable and be stratified by whether pts were chosen to receive induction CT (Yes/No) and time since adjuvant hormone therapy ( Disclosure G. Arpino: I declare that I have participated in an advisory board for GSK. C. Poole: I declare that have served on a advisory board and received research finding from F. Hoffmann-La Roche. L. Mitchell: I am currently employed by F. Hoffmann-La Roche. C. Pelizon: I am currently employed by F. Hoffmann-La Roche. M.F. Rimawi: I declare that have received research funding from Genentech Inc and GSK. All other authors have declared no conflicts of interest.