Trastuzumab plus capecitabine with or without pertuzumab in patients with HER2-positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA).

Abstract

TPS118 Background: Pertuzumab (P) is a promising new anti-HER2 antibody which has shown both activity and good tolerability when combined with trastuzumab (H) in patients with HER2-positive breast cancer. Capecitabine (X) in combination with H has been shown to be more efficacious than X alone as second-line treatment of patients with HER2-positive metastatic breast cancer (MBC). The PHEREXA study is designed to investigate the potential benefit of administering P and H combined with X in patients with HER2-positive MBC whose disease has progressed during or following H-based therapy for first-line MBC. Methods: In this multicenter, open-label, Phase II trial (NCT01026142), patients are randomized 1:1 to Arm A (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose; X: 1250 mg/m2 twice daily for 14d q3w) or Arm B (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose; X: 1000 mg/m2 twice daily for 14d; P: 840 mg loading dose and 420 mg thereafter q3w). Enrolment began in January 2010 and 450 patients are to be recruited from ~130 sites in 19 countries. Eligible patients must have HER2-positive MBC (fluorescence or chromogenic in situ hybridization-positive and/or immunohistochemistry 3+), which has progressed during or following H-based therapy for first-line MBC, prior taxane, and left ventricular ejection fraction (LVEF) ≥50% at baseline. Exclusion criteria include prior treatment with X or P, concurrent immunotherapy or hormonal anticancer therapy, and history of LVEF decline to <50% during prior H-based therapy. The primary endpoint is progression-free survival (PFS; independent assessment). Secondary endpoints include overall survival, PFS (investigator assessment), safety/tolerability. It is planned that a panel of biomarkers including HER 1, 2 and 3 receptor status and downstream markers will be analysed. No untoward safety signals have yet been identified. There are currently 58 patients randomized in the study (as of 13 January 2011).