Ariadna Tibau1, Laura Díez-González2, Beatriz Navarro3, Eva M Galán-Moya2, Arnoud J Templeton4, Bostjan Seruga5, Atanasio Pandiella6, Eitan Amir7, Alberto Ocana8,9,10. 1. Hospital Santa Crau y Sant Pau, Barcelona, Spain. 2. Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain. 3. Clinical Research Support Unit, Albacete University Hospital, Albacete and Fundación Hospital Nacional de Paraplejicos, Toledo, Spain. 4. Department of Medical Oncology and Hematology, St. Claraspital, Basel, Switzerland. 5. Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia. 6. IBMCC-CSIC, Universidad de Salamanca, Salamanca, Spain. 7. Divisions of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 8. Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain. albertoo@sescam.jccm.es. 9. 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. 10. Regional Biomedical Research Center (CRIB), Castilla La Mancha University, Albacete, Spain. albertoo@sescam.jccm.es.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Ben Tran; Janet E Dancey; Suzanne Kamel-Reid; John D McPherson; Philippe L Bedard; Andrew M K Brown; Tong Zhang; Patricia Shaw; Nicole Onetto; Lincoln Stein; Thomas J Hudson; Benjamin G Neel; Lillian L Siu Journal: J Clin Oncol Date: 2012-01-23 Impact factor: 44.544
Authors: David R Parkinson; Robert T McCormack; Susan M Keating; Steven I Gutman; Stanley R Hamilton; Elizabeth A Mansfield; Margaret A Piper; Patricia Deverka; Felix W Frueh; J Milburn Jessup; Lisa M McShane; Sean R Tunis; Caroline C Sigman; Gary J Kelloff Journal: Clin Cancer Res Date: 2014-03-15 Impact factor: 12.531
Authors: Alice T Shaw; Dong-Wan Kim; Kazuhiko Nakagawa; Takashi Seto; Lucio Crinó; Myung-Ju Ahn; Tommaso De Pas; Benjamin Besse; Benjamin J Solomon; Fiona Blackhall; Yi-Long Wu; Michael Thomas; Kenneth J O'Byrne; Denis Moro-Sibilot; D Ross Camidge; Tony Mok; Vera Hirsh; Gregory J Riely; Shrividya Iyer; Vanessa Tassell; Anna Polli; Keith D Wilner; Pasi A Jänne Journal: N Engl J Med Date: 2013-06-01 Impact factor: 91.245
Authors: Ben Tran; Andrew M K Brown; Philippe L Bedard; Eric Winquist; Glenwood D Goss; Sebastien J Hotte; Stephen A Welch; Hal W Hirte; Tong Zhang; Lincoln D Stein; Vincent Ferretti; Stuart Watt; Wei Jiao; Karen Ng; Sangeet Ghai; Patricia Shaw; Teresa Petrocelli; Thomas J Hudson; Benjamin G Neel; Nicole Onetto; Lillian L Siu; John D McPherson; Suzanne Kamel-Reid; Janet E Dancey Journal: Int J Cancer Date: 2012-10-11 Impact factor: 7.396