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Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer.

Publication ,  Journal Article
Sonpavde, G; Pond, GR; Armstrong, AJ; Galsky, MD; Leopold, L; Wood, BA; Wang, S-L; Paolini, J; Chen, I; Chow-Maneval, E; Mooney, DJ; Smith, MR ...
Published in: BJU Int
December 2014

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.

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Published In

BJU Int

DOI

EISSN

1464-410X

Publication Date

December 2014

Volume

114

Issue

6b

Start / End Page

E25 / E31

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Time Factors
  • Taxoids
  • Survival Rate
  • Sunitinib
  • Retrospective Studies
  • Radiography
  • Pyrroles
  • Prostatic Neoplasms, Castration-Resistant
  • Prednisone
 

Citation

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Sonpavde, G., Pond, G. R., Armstrong, A. J., Galsky, M. D., Leopold, L., Wood, B. A., … Michaelson, M. D. (2014). Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer. BJU Int, 114(6b), E25–E31. https://doi.org/10.1111/bju.12589
Sonpavde, Guru, Gregory R. Pond, Andrew J. Armstrong, Matthew D. Galsky, Lance Leopold, Brian A. Wood, Shaw-Ling Wang, et al. “Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer.BJU Int 114, no. 6b (December 2014): E25–31. https://doi.org/10.1111/bju.12589.
Sonpavde G, Pond GR, Armstrong AJ, Galsky MD, Leopold L, Wood BA, Wang S-L, Paolini J, Chen I, Chow-Maneval E, Mooney DJ, Lechuga M, Smith MR, Michaelson MD. Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer. BJU Int. 2014 Dec;114(6b):E25–E31.

Published In

BJU Int

DOI

EISSN

1464-410X

Publication Date

December 2014

Volume

114

Issue

6b

Start / End Page

E25 / E31

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Time Factors
  • Taxoids
  • Survival Rate
  • Sunitinib
  • Retrospective Studies
  • Radiography
  • Pyrroles
  • Prostatic Neoplasms, Castration-Resistant
  • Prednisone