title: Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.
abstract: Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development.
  
  
  
  Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug.
  
  
  
  We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies.
  
  
  
  The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.
authors.affiliation: Hospital Santa Crau y Sant Pau, Barcelona, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Tibau
authors.affiliation: Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Díez-González
authors.affiliation: Clinical Research Support Unit, Albacete University Hospital, Albacete and Fundación Hospital Nacional de Paraplejicos, Toledo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Navarro
authors.affiliation: Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Galán-Moya
authors.affiliation: Department of Medical Oncology and Hematology, St. Claraspital, Basel, Switzerland.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Seruga
authors.affiliation: IBMCC-CSIC, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.affiliation: Divisions of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain. albertoo@sescam.jccm.es.|Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, 02006, Albacete, Spain. albertoo@sescam.jccm.es.|Regional Biomedical Research Center (CRIB), Castilla La Mancha University, Albacete, Spain. albertoo@sescam.jccm.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocana
mesh_terms: D000970:Antineoplastic Agents; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D006801:Humans; D025202:Molecular Diagnostic Techniques; D009369:Neoplasms / Q000188:drug therapy; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents