CHICAGO–The Prostate Cancer Working Group 3 (PCWG3) recommendations will guide clinical trial design and conduct for therapeutics being tested in both M0 and M1 castration-resistant prostate cancer (CRPC) patient populations, according to a consensus criteria update presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.
The new criteria are based upon new evidence from clinical trial data and validation studies of PCWG2 guidelines.
“PCWG3 considers all aspects of the clinical trial process from discovery to validation in a biomarker context,” said Howard I. Scher, MD, Chair of PCWG3.
With respect to eligibility, the PCWG3 defines clinical phenotypes and molecular genotypes for risk stratification and to predict likelihood of response to treatment. Furthermore, the PCWG3 revised a clinical states model to account for the effect of prior therapy/therapies on disease biology.
In regard to the intervention aspect of the clinical trial, the guidelines state that there should be proof of mechanism, dose, and schedule. Pharmacodynamic measures should be used to confirm the mechanism of action, and dose and schedule should be optimized for further study based on biologic markers and safety.
The PCWG3 recommendations add a new facet to outcomes and endpoints: symptomatic skeletal events. In addition to evaluating clinical benefit, symptomatic skeletal events, which is inclusive of palliative radiation or surgery to bone, spinal cord compression, or pathologic clinical fracture, should be included as an endpoint.
For patients transitioning from M0 to M1 disease, metastasis-free survival and radiographic progression-free survival should be used as endpoints, as well.
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Speaking about recognizing the heterogeneity of the disease, Dr. Scher said, “PCWG3 draws the distinction between documenting and recording the date of progression in an individual disease manifestation for consistency of reporting versus the decision to stop therapy.”
“These recommendations will guide clinical trial design and conduct for therapeutics being tested in both M0 and M1 CRPC patient populations,” Dr. Scher concluded.
The recommendations will be submitted for publication within the coming months.
1. Scher HI, Morris MJ, Stadler WM, et al. The Prostate Cancer Working Group 3 (PCWG3) consensus for trials in castration-resistant prostate cancer (CRPC). J Clin Oncol. 2015;33:(suppl; abstr 5000).