MedStar Authors catalog › Details for: 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.
Citation: Journal of Clinical Oncology. 32(33):3753-61, 2014 Nov 20..Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology.ISSN: 0732-183X.Full author list: Baselga J; Cortes J; Im SA; Clark E; Ross G; Kiermaier A; Swain SM.UI/PMID: 25332247.Subject(s): *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use] | *Antineoplastic Agents/tu [Therapeutic Use] | Breast Neoplasms/bl [Blood] | Breast Neoplasms/ch [Chemistry] | *Breast Neoplasms/dt [Drug Therapy] | Breast Neoplasms/mo [Mortality] | Double-Blind Method | Female | Humans | Mutation | Neoplasm Metastasis | Phosphatidylinositol 3-Kinases/ge [Genetics] | Prognosis | Prospective Studies | *Receptor, ErbB-2/an [Analysis] | Receptors, Estrogen/an [Analysis] | *Tumor Markers, Biological/an [Analysis]Institution(s): Washington Cancer InstituteActivity type: Journal Article.Medline article type(s): Clinical Trial, Phase III | Journal Article | Randomized Controlled Trial | Research Support, Non-U.S. Gov'tOnline resources: Click here to access onlineDigital Object Identifier: http://dx.doi.org/10.1200/JCO.2013.54.5384 (Click here)Abbreviated citation: J Clin Oncol. 32(33):3753-61, 2014 Nov 20.Local Holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008.Abstract: 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.Abstract: 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).Abstract: 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).Abstract: 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.