José Baselga1, Javier Cortés2, Seock-Ah Im2, Emma Clark2, Graham Ross2, Astrid Kiermaier2, Sandra M Swain2. 1. José Baselga, Memorial Sloan Kettering Cancer Center, New York, NY; Javier Cortés, Vall d'Hebron University Hospital, Barcelona, Spain; Seock-Ah Im, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Emma Clark and Graham Ross, Roche Products, Welwyn Garden City, United Kingdom; Astrid Kiermaier, F. Hoffmann-La Roche, Basel, Switzerland; and Sandra M. Swain, Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC. baselgaj@mskcc.org. 2. José Baselga, Memorial Sloan Kettering Cancer Center, New York, NY; Javier Cortés, Vall d'Hebron University Hospital, Barcelona, Spain; Seock-Ah Im, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Emma Clark and Graham Ross, Roche Products, Welwyn Garden City, United Kingdom; Astrid Kiermaier, F. Hoffmann-La Roche, Basel, Switzerland; and Sandra M. Swain, Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC.
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. 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 FCγR 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). 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 HER3mRNA 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). 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.
RCT Entities:
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. 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 FCγR 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). 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). 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.
Authors: Asunción Díaz-Serrano; Barbara Angulo; Carolina Dominguez; Roberto Pazo-Cid; Antonieta Salud; Paula Jiménez-Fonseca; Ana Leon; Maria Carmen Galan; Maria Alsina; Fernando Rivera; J Carlos Plaza; Luis Paz-Ares; Fernando Lopez-Rios; Carlos Gómez-Martín Journal: Oncologist Date: 2018-04-26
Authors: Rim S Kim; Nan Song; Patrick G Gavin; Roberto Salgado; Hanna Bandos; Zuzana Kos; Giuseppe Floris; Gert G G M Van den Eynden; Sunil Badve; Sandra Demaria; Priya Rastogi; Louis Fehrenbacher; Eleftherios P Mamounas; Sandra M Swain; D Lawrence Wickerham; Joseph P Costantino; Soonmyung Paik; Norman Wolmark; Charles E Geyer; Peter C Lucas; Katherine L Pogue-Geile Journal: J Natl Cancer Inst Date: 2019-08-01 Impact factor: 13.506
Authors: Stephen J Luen; Roberto Salgado; Stephen Fox; Peter Savas; Jennifer Eng-Wong; Emma Clark; Astrid Kiermaier; Sandra M Swain; Jose Baselga; Stefan Michiels; Sherene Loi Journal: Lancet Oncol Date: 2016-12-07 Impact factor: 41.316
Authors: Manish A Shah; Yoon-Koo Kang; Peter C Thuss-Patience; Atsushi Ohtsu; Jaffer A Ajani; Eric Van Cutsem; Silke Hoersch; Marie-Laurence Harle-Yge; Sanne Lysbet de Haas Journal: Gastric Cancer Date: 2019-01-31 Impact factor: 7.370