Impact of availability of companion diagnostics on the clinical development of anticancer drugs

[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.
Instituto de Salud Carlos III (PI16/01121), ACEPAIN; Diputación de Albacete and CRIS Cancer Foundation (to AO); Beca Ampliación de Estudios (BAE) to AO for his stay at Yale University; Ministry of Economy and Competitiveness of Spain (BFU2012–39151 and BFU2015-71371-R), the Instituto de Salud Carlos III through the Spanish Cancer Centers Network Program (RD12/0036/0003) and the CIBERONC, the scientific foundation of the Asociación Española Contra el Cáncer (AECC) and the CRIS Foundation (to AP). The work carried out in the Spanish laboratories receives support from the European Community through the regional development funding program (FEDER).