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- Title
Radiographic progression by Prostate Cancer Working Group ( PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer.
- Authors
Sonpavde, Guru; Pond, Gregory R.; Armstrong, Andrew J.; Galsky, Matthew D.; Leopold, Lance; Wood, Brian A.; Wang, Shaw‐Ling; Paolini, Jolanda; Chen, Isan; Chow‐Maneval, Edna; Mooney, David J.; Lechuga, Mariajose; Smith, Matthew R.; Michaelson, M. Dror
- Abstract
Objective To investigate the association of radiographic progression defined by Prostate Cancer Working Group ( PCWG)-2 guidelines and overall survival ( OS) in men with metastatic castration-resistant prostate cancer ( mCRPC). Patients and Methods Two trials that used PCWG-2 guidelines to define progression were analysed: a randomized phase II trial ( n = 221) comparing first-line docetaxel-prednisone plus AT-101 or placebo, and a phase III trial ( n = 873) comparing prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox proportional hazards regression models were used to estimate the association of radiographic progression with OS. Landmark analyses compared progressing patients with those who had not progressed. Sub-analyses compared patients removed from trial for progression vs other reasons. Results An increased risk of death was seen for radiographic progression at landmark times from 6 to 12 months with docetaxel-based therapy (hazard ratio [ HR] >1.7 at all time-points). An increased risk of death was also seen with post-docetaxel prednisone alone or with sunitinib for progression at landmark times from 2 to 8 months ( HR >2.7 at all time-points). Kendall's τ was 0.50 ( P < 0.001) in the setting of docetaxel-based therapy and 0.34 ( P < 0.001) in the post-docetaxel setting for association between radiographic progression and death amongst patients with both events. Removal from study due to radiographic progression was associated with a significantly lower OS compared with removal for other reasons in both trials. Limitations of a retrospective analysis apply and there was no central radiology review. Conclusions Radiographic progression by PCWG-2 criteria was significantly associated with OS in patients with mCRPC receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. With external validation as a surrogate endpoint in trials showing survival benefits, the use of radiographic progression-free survival may expedite drug development in mCRPC, which has been hampered by the lack of intermediate endpoints.
- Subjects
PROSTATE cancer; DOCETAXEL; PROPORTIONAL hazards models; PREDNISONE; RADIOGRAPHY
- Publication
BJU International, 2014, Vol 114, Issue 6b, pE25
- ISSN
1464-4096
- Publication type
Article
- DOI
10.1111/bju.12589