Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy.

Published

Journal Article

PURPOSE: Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy. PATIENTS AND METHODS: Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy. RESULTS: The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a ≥ 30% decline in PSA was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43 to 0.64; P < .001). Adjusting for treatment effect, the HR for a ≥ 30% PSA decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained statistically significant, thus failing the third Prentice criterion. The PTE for a ≥ 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of surrogacy for OS. The values of R(2) were < 1, suggesting that PSA decline was not surrogate for OS. CONCLUSION: Surrogacy for any PSA-based end point could not be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes.

Full Text

Duke Authors

Cited Authors

  • Halabi, S; Armstrong, AJ; Sartor, O; de Bono, J; Kaplan, E; Lin, C-Y; Solomon, NC; Small, EJ

Published Date

  • November 1, 2013

Published In

Volume / Issue

  • 31 / 31

Start / End Page

  • 3944 - 3950

PubMed ID

  • 24101043

Pubmed Central ID

  • 24101043

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2013.50.3201

Language

  • eng

Conference Location

  • United States