Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3 Journal Article

Authors: Scher, H. I.; Morris, M. J.; Stadler, W. M.; Higano, C.; Basch, E.; Fizazi, K.; Antonarakis, E. S.; Beer, T. M.; Carducci, M. A.; Chi, K. N.; Corn, P. G.; De Bono, J. S.; Dreicer, R.; George, D. J.; Heath, E. I.; Hussain, M.; Kelly, W. K.; Liu, G.; Logothetis, C.; Nanus, D.; Stein, M. N.; Rathkopf, D. E.; Slovin, S. F.; Ryan, C. J.; Sartor, O.; Small, E. J.; Smith, M. R.; Sternberg, C. N.; Taplin, M. E.; Wilding, G.; Nelson, P. S.; Schwartz, L. H.; Halabi, S.; Kantoff, P. W.; Armstrong, A. J.
Article Title: Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3
Abstract: Purpose Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups. Methods An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations. Results PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials. Conclusion PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 12
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-04-20
Start Page: 1402
End Page: 1418
Language: English
DOI: 10.1200/jco.2015.64.2702
PROVIDER: scopus
PMCID: PMC4872347
PUBMED: 26903579
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Susan Slovin
    178 Slovin
  2. Michael Morris
    256 Morris
  3. Dana Elizabeth Rathkopf
    134 Rathkopf
  4. Howard Scher
    771 Scher