Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer.
Publication details: 2014; ISSN:- 0732-183X
- *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
- *Antineoplastic Agents/tu [Therapeutic Use]
- *Breast Neoplasms/dt [Drug Therapy]
- *Receptor, ErbB-2/an [Analysis]
- *Tumor Markers, Biological/an [Analysis]
- Breast Neoplasms/bl [Blood]
- Breast Neoplasms/ch [Chemistry]
- Breast Neoplasms/mo [Mortality]
- Double-Blind Method
- Female
- Humans
- Mutation
- Neoplasm Metastasis
- Phosphatidylinositol 3-Kinases/ge [Genetics]
- Prognosis
- Prospective Studies
- Receptors, Estrogen/an [Analysis]
- Washington Cancer Institute
- Clinical Trial, Phase III
- Journal Article
- Randomized Controlled Trial
- Research Support, Non-U.S. Gov't
| Item type | Current library | Collection | Call number | Status | Date due | Barcode | |
|---|---|---|---|---|---|---|---|
| Journal Article | MedStar Authors Catalog | Article | 25332247 | Available | 25332247 |
Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008
CONCLUSION: Through comprehensive prospective analyses, CLEOPATRA biomarker data demonstrate that HER2 is the only marker suited for patient selection for the trastuzumab plus pertuzumab-based regimen in HER2-positive metastatic breast cancer. HER2, HER3, and PIK3CA were relevant prognostic factors.Copyright � 2014 by American Society of Clinical Oncology.
PATIENTS AND METHODS: Mandatory tumor and serum samples were collected (N = 808; 58% to 99.8% were assessable), and amphiregulin, betacellulin, epidermal growth factor (EGF), transforming growth factor alpha, EGF receptor, HER2, HER3, insulin-like growth factor 1 receptor, PTEN, phosphorylated AKT, PIK3CA, CMYC, serum HER2 extracellular domain (sHER2), and FCR were assessed using appropriate assays. Two types of correlations were investigated using univariable Cox regression: predictive effects (qualitative association of biomarkers with pertuzumab progression-free survival [PFS] benefit) and prognostic effects independent of treatment arm (relationship of each biomarker to clinical outcome in both arms pooled).
PURPOSE: To explore the prognostic and/or predictive value of human epidermal growth factor receptor 2 (HER2) pathway-related biomarkers in the phase III CLEOPATRA study of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer.
RESULTS: Pertuzumab consistently showed a PFS benefit, independent of biomarker subgroups (hazard ratio < 1.0), including estrogen receptor-negative and -positive subgroups. High HER2 protein, high HER2 and HER3 mRNA levels, wild-type PIK3CA, and low sHER2 showed a significantly better prognosis (P < .05). PIK3CA showed the greatest prognostic effect, with longer median PFS for patients whose tumors expressed wild-type versus mutated PIK3CA in both the control (13.8 v 8.6 months) and pertuzumab groups (21.8 v 12.5 months).
English