title: Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov.
abstract: The aim of this study was to describe pharmacogenomics-based inclusion criteria (enrichment) and the main characteristics of clinical trials involving oncology-targeted therapies.
  
  
  
  Clinical trials of oncology-targeted therapies approved after 2005 with pharmacogenomic testing required or recommended in their label were retrieved from a mapping of the ClinicalTrials.gov database.
  
  
  
  We examined information for 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) were enriched on another biomarker, whereas 270 trials (31%) included all patients. The median proportion of trials corresponding to both the drug's indication and drug's target was 35%. Of the 361 trials that tested drugs in another disease than the first one in the label, 219 (61%) were without enrichment and 87 (24%) were actually enriched but on another biomarker than the first one in the label.
  
  
  
  Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most targeted therapies have been developed only using biomarker-positive patients; therefore, exclusion of biomarker-negative patients from treatment relies on only preclinical data and on biological understanding of the disease and target.Genet Med 18 8, 796-805.
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vivot
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Li
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.
authors.forename: Jean-David
authors.initials: JD
authors.lastname: Zeitoun
authors.affiliation: Department of Pharmacology-Genetics, Assistance Publique des Hôpitaux de Paris (AP-HP), Saint-Louis Hospital, Paris, France.|INSERM UMRS 976, Paris, France.
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Crequit
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.|Faculté de Médecine, Université Paris Descartes, Paris, France.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Hôtel Dieu, Centre d'Épidémiologie Clinique, Paris, France.|INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (CRESS), METHODS Team, Paris Descartes University, Paris, France.|Faculté de Médecine, Université Paris Descartes, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002986:Clinical Trials as Topic; D004348:Drug Labeling; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000071184:Pharmacogenomic Variants; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor