Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer

Andrew J. Armstrong, Elizabeth Garrett-Mayer, Yi Chun Ou Yang, Michael A Carducci, Ian Tannock, Ronald De Wit, Mario Eisenberger

Research output: Contribution to journalArticle

Abstract

Purpose: It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods: In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results: A ≥ 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion: In the TAX327 trial, a PSA decline of ≥ 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.

Original languageEnglish (US)
Pages (from-to)3965-3970
Number of pages6
JournalJournal of Clinical Oncology
Volume25
Issue number25
DOIs
StatePublished - Sep 1 2007

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Prostate-Specific Antigen
Prostatic Neoplasms
Hormones
Pain
Survival
docetaxel
Therapeutics
Mitoxantrone
Cytotoxins
Prednisone
Proportional Hazards Models
Appointments and Schedules
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. / Armstrong, Andrew J.; Garrett-Mayer, Elizabeth; Yang, Yi Chun Ou; Carducci, Michael A; Tannock, Ian; De Wit, Ronald; Eisenberger, Mario.

In: Journal of Clinical Oncology, Vol. 25, No. 25, 01.09.2007, p. 3965-3970.

Research output: Contribution to journalArticle

Armstrong, Andrew J. ; Garrett-Mayer, Elizabeth ; Yang, Yi Chun Ou ; Carducci, Michael A ; Tannock, Ian ; De Wit, Ronald ; Eisenberger, Mario. / Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 25. pp. 3965-3970.
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abstract = "Purpose: It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods: In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results: A ≥ 30{\%} PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95{\%} CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95{\%} CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30{\%} PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion: In the TAX327 trial, a PSA decline of ≥ 30{\%} within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.",
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AU - Tannock, Ian

AU - De Wit, Ronald

AU - Eisenberger, Mario

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N2 - Purpose: It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods: In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results: A ≥ 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion: In the TAX327 trial, a PSA decline of ≥ 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.

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