title: CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C485206:pertuzumab