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J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.

Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.

Author information

1
Howard I. Scher, Michael J. Morris, Dana E. Rathkopf, and Susan F. Slovin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College; David Nanus, NewYork Presbyterian Weill Cornell Medical Center; Lawrence W. Schwartz, NewYork Presbyterian Columbia University Medical Center, New York, NY; Walter M. Stadler, University of Chicago Medicine, Chicago, IL; Celestina Higano and Peter S. Nelson, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA; Ethan Basch, University of North Carolina at Chapel Hill, Chapel Hill, NC; Emmanual S. Antonarakis and Michael A. Carducci, Johns Hopkins University School of Medicine, Baltimore, MD; Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Paul G. Corn and Christopher Logothetis, MD Anderson Cancer Center, Houston, TX; Robert Dreicer, University of Virginia School of Medicine, Charlottesville, VA; Daniel J. George, Susan Halabi, and Andrew J. Armstrong, Duke University and Duke Cancer Institute, Durham, NC; Elisabeth I. Heath, Wayne State University Karmanos Cancer Institute, Detroit; and Maha Hussain, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Wm. Kevin Kelly, Sidney Kimmel School of Medicine at Thomas Jefferson University, Philadelphia, PA; Glenn Liu and George Wilding, University of Wisconsin Carbone Cancer Center, Madison, WI; Mark N. Stein, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ; Charles S. Ryan and Eric J. Small, University of California Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Oliver Sartor, Tulane School of Medicine, New Orleans, LA; Matthew Raymond Smith, Massachusetts General Hospital Cancer Center and Harvard Medical School; Mary-Ellen Taplin and Philip W. Kantoff, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif, Franc

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.

PMID:
26903579
PMCID:
PMC4872347
[Available on 2017-02-20]
DOI:
10.1200/JCO.2015.64.2702
[Indexed for MEDLINE]
Free PMC Article

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