Skip to main content
SpringerLink
Log in

Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  2. Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501:355–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Amir E, Seruga B, Martinez-Lopez J, et al. Oncogenic targets, magnitude of benefit, and market pricing of antineoplastic drugs. J Clin Oncol. 2011;29:2543–9.

    Article  PubMed  Google Scholar 

  4. Tran B, Brown AM, Bedard PL, et al. Feasibility of real time next generation sequencing of cancer genes linked to drug response: results from a clinical trial. Int J Cancer. 2013;132:1547–55.

    Article  CAS  PubMed  Google Scholar 

  5. Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339:1546–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tran B, Dancey JE, Kamel-Reid S, et al. Cancer genomics: technology, discovery, and translation. J Clin Oncol. 2012;30:647–60.

    Article  PubMed  Google Scholar 

  7. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.

    Article  CAS  PubMed  Google Scholar 

  8. Mansfield EA. FDA perspective on companion diagnostics: an evolving paradigm. Clin Cancer Res. 2014;20:1453–7.

    Article  CAS  PubMed  Google Scholar 

  9. Ocana A, Amir E, Yeung C, et al. How valid are claims for synergy in published clinical studies? Ann Oncol. 2012;23:2161–6.

    Article  CAS  PubMed  Google Scholar 

  10. Ocana A, Pandiella A, Siu LL, Tannock IF. Preclinical development of molecular-targeted agents for cancer. Nat Rev Clin Oncol. 2010;8:200–9.

    Article  PubMed  Google Scholar 

  11. US FDA. Hematology/oncology (cancer) approvals and safety notifications. http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm. Accessed 1 Jan 2014.

  12. CenterWatch. 2017 FDA approved drugs. http://www.centerwatch.com/drug-information/fda-approved-drugs/year/. Accessed 1 Jan 2014.

  13. Drugs@FDA: FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Addlsearch_drug_name. Accessed 1 Jan 2014.

  14. Parkinson DR, McCormack RT, Keating SM, et al. Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer. Clin Cancer Res. 2014;20:1428–44.

    Article  CAS  PubMed  Google Scholar 

  15. Willyard C. ‘Basket studies’ will hold intricate data for cancer drug approvals. Nat Med. 2013;19:655.

    Article  CAS  PubMed  Google Scholar 

  16. Jorgensen JT. Clinical application of companion diagnostics. Trends Mol Med. 2015;21:405–7.

    Article  PubMed  Google Scholar 

  17. Manji A, Brana I, Amir E, et al. Evolution of clinical trial design in early drug development: systematic review of expansion cohort use in single-agent phase I cancer trials. J Clin Oncol. 2013;31:4260–7.

    Article  CAS  PubMed  Google Scholar 

  18. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–62.

    Article  CAS  PubMed  Google Scholar 

  19. European Organisation for Research and Treatment of Cancer—EORTC. CREATE: cross-tumoral phase 2 with crizotinib (CREATE). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01524926. Accessed 1 Jan 2014.

Download references

Acknowledgements

Asociación ACEPAIN for their support in cancer research.

Author information

Authors and Affiliations

  1. Hospital Santa Crau y Sant Pau, Barcelona, Spain

    Ariadna Tibau

  2. Translational Research Unit, CIBERONC, Albacete University Hospital, Albacete, Spain

    Laura Díez-González, Eva M. Galán-Moya & Alberto Ocana

  3. Clinical Research Support Unit, Albacete University Hospital, Albacete and Fundación Hospital Nacional de Paraplejicos, Toledo, Spain

    Beatriz Navarro

  4. Department of Medical Oncology and Hematology, St. Claraspital, Basel, Switzerland

    Arnoud J. Templeton

  5. Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    Bostjan Seruga

  6. IBMCC-CSIC, Universidad de Salamanca, Salamanca, Spain

    Atanasio Pandiella

  7. Divisions of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

    Eitan Amir

  8. Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, 02006, Albacete, Spain

    Alberto Ocana

  9. Regional Biomedical Research Center (CRIB), Castilla La Mancha University, Albacete, Spain

    Alberto Ocana

Authors
  1. Ariadna Tibau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Díez-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beatriz Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eva M. Galán-Moya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arnoud J. Templeton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bostjan Seruga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Atanasio Pandiella
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eitan Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alberto Ocana
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Ocana.

Ethics declarations

Conflict of interest

Ariadna Tibau, Laura Díez-González, Beatriz Navarro, Eva M. Galán-Moya, Arnoud J. Templeton, Bostjan Seruga, Atanasio Pandiella, Eitan Amir, and Alberto Ocana have no conflicts of interest to declare.

Funding

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).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 144 kb)

Supplementary material 2 (PDF 436 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tibau, A., Díez-González, L., Navarro, B. et al. Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs. Mol Diagn Ther 21, 337–343 (2017). https://doi.org/10.1007/s40291-017-0267-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-017-0267-y

Keywords

Search

Navigation