Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group
Howard I Scher, Susan Halabi, Ian Tannock, Michael Morris, Cora N Sternberg, Michael A Carducci, Mario A Eisenberger, Celestia Higano, Glenn J Bubley, Robert Dreicer, Daniel Petrylak, Philip Kantoff, Ethan Basch, William Kevin Kelly, William D Figg, Eric J Small, Tomasz M Beer, George Wilding, Alison Martin, Maha Hussain, Prostate Cancer Clinical Trials Working Group, Howard I Scher, Susan Halabi, Ian Tannock, Michael Morris, Cora N Sternberg, Michael A Carducci, Mario A Eisenberger, Celestia Higano, Glenn J Bubley, Robert Dreicer, Daniel Petrylak, Philip Kantoff, Ethan Basch, William Kevin Kelly, William D Figg, Eric J Small, Tomasz M Beer, George Wilding, Alison Martin, Maha Hussain, Prostate Cancer Clinical Trials Working Group
Abstract
Purpose: To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone.
Methods: A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data.
Results: The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or "no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group.
Conclusion: PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.
Conflict of interest statement
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: Ian Tannock, sanofi-aventis (U), Algeta ASA (U), GPC Biotech (U); Michael A. Carducci, Abbott Laboratories (C), sanofi-aventis (U), Methylgene (C), Cougar Biotech (C); Mario A. Eisenberger, sanofi-aventis (C), GPC (C), Celgene (C); Robert Dreicer, Merck (C), sanofi-aventis (C), Bristol-Myers Squibb (C); Daniel Petrylak, Aventis (C), GPC Biotech (C), Abbott Laboratories (C); Eric J. Small, Cougar Biotechnology (C), Poniard Pharmaceuticals (C); Tomasz M. Beer, Novacea (C) Stock Ownership: Tomasz M. Beer, Novacea Honoraria: Michael A. Carducci, sanofi-aventis, Abbott Laboratories; Mario A. Eisenberger, sanofi-aventis, Ipsen, GPC; Robert Dreicer, Berlex; Daniel Petrylak, Aventis, Celegene, Abbott; William Kevin Kelly, sanofi-aventis, Genetech; Tomasz M. Beer, sanofi-aventis Research Funding: Ian Tannock, sanofi-aventis, Novacea; Mario A. Eisenberger, sanofi-aventis, Clegene, Cytogen; Robert Dreicer, sanofi-aventis, Eli Lilly, Millenium; Daniel Petrylak, Aventis, Celegene, GPC Biotech; William Kevin Kelly, sanofi-aventis, Genetech, Curagen; Eric J. Small, Dendreon, Novartis; Tomasz M. Beer, sanofi-aventis Expert Testimony: None Other Remuneration: None
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Source: PubMed