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

Publication ,  Journal Article
Halabi, S; Armstrong, AJ; Sartor, O; de Bono, J; Kaplan, E; Lin, C-Y; Solomon, NC; Small, EJ
Published in: J Clin Oncol
November 1, 2013

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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 1, 2013

Volume

31

Issue

31

Start / End Page

3944 / 3950

Location

United States

Related Subject Headings

  • Taxoids
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mitoxantrone
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans
 

Citation

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Halabi, S., Armstrong, A. J., Sartor, O., de Bono, J., Kaplan, E., Lin, C.-Y., … Small, E. J. (2013). Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy. J Clin Oncol, 31(31), 3944–3950. https://doi.org/10.1200/JCO.2013.50.3201
Halabi, Susan, Andrew J. Armstrong, Oliver Sartor, Johann de Bono, Ellen Kaplan, Chen-Yen Lin, Nicole C. Solomon, and Eric J. Small. “Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy.J Clin Oncol 31, no. 31 (November 1, 2013): 3944–50. https://doi.org/10.1200/JCO.2013.50.3201.
Halabi S, Armstrong AJ, Sartor O, de Bono J, Kaplan E, Lin C-Y, et al. Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy. J Clin Oncol. 2013 Nov 1;31(31):3944–50.
Halabi, Susan, et al. “Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy.J Clin Oncol, vol. 31, no. 31, Nov. 2013, pp. 3944–50. Pubmed, doi:10.1200/JCO.2013.50.3201.
Halabi S, Armstrong AJ, Sartor O, de Bono J, Kaplan E, Lin C-Y, Solomon NC, Small EJ. Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy. J Clin Oncol. 2013 Nov 1;31(31):3944–3950.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 1, 2013

Volume

31

Issue

31

Start / End Page

3944 / 3950

Location

United States

Related Subject Headings

  • Taxoids
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mitoxantrone
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans