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.

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Citation: Journal of Clinical Oncology. 32(33):3753-61, 2014 Nov 20.PMID: 25332247Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Clinical Trial, Phase III | Journal Article | Randomized Controlled Trial | Research Support, Non-U.S. Gov'tSubject headings: *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]Year: 2014Local holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008ISSN:
  • 0732-183X
Name of journal: Journal of clinical oncology : official journal of the American Society of Clinical OncologyAbstract: 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).All authors: Baselga J, Clark E, Cortes J, Im SA, Kiermaier A, Ross G, Swain SMFiscal year: FY2015Digital Object Identifier: Date added to catalog: 2015-03-17
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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).

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