INTRODUCTION: Patients with human epidermal growth factor receptor 2 
(HER2)-positive breast cancer have a poor prognosis. Despite proven efficacy 
with the standard of care, trastuzumab, most patients with HER2-positive 
metastatic breast cancer (MBC) will eventually progress, requiring further 
intervention to prolong life. Pertuzumab, a humanized monoclonal antibody, is 
the first HER2 dimerization inhibitor. It binds to the dimerization site on the 
HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, 
thus inhibiting tumor cell growth and survival. Combining trastuzumab and 
pertuzumab therefore provides a more comprehensive blockade of the HER signaling 
pathways, resulting in greater antitumor efficacy.
STUDY DESIGN: CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is 
an international, randomized, double-blind, placebo-controlled phase III trial 
that aims to recruit approximately 800 patients from around 250 centers 
worldwide. Adults with HER2-positive adenocarcinoma of the breast with locally 
recurrent or metastatic disease will be randomized (1:1) to receive docetaxel, 
trastuzumab, and pertuzumab or docetaxel, trastuzumab, and placebo. The primary 
endpoint of the study is progression-free survival (PFS), based on tumor 
assessments conducted by an independent review facility. Secondary endpoints 
include PFS evaluated by investigator assessment, overall survival, objective 
response rate, duration of response, time to symptom progression, and safety. 
Data will also be collected to identify biomarkers that may correlate with 
clinical outcomes.
CONCLUSION: The CLEOPATRA study will provide important information about the 
efficacy and safety of adding pertuzumab to one current standard of care in 
patients with HER2-positive MBC.