CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer

Clin Breast Cancer. 2010 Dec 1;10(6):489-91. doi: 10.3816/CBC.2010.n.065.


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.

Trial registration: NCT00567190.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Signal Transduction / drug effects
  • Taxoids / administration & dosage
  • Time Factors
  • Trastuzumab
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Taxoids
  • Docetaxel
  • Receptor, ErbB-2
  • pertuzumab
  • Trastuzumab

Associated data