Risk of development of visceral metastases subsequent to abiraterone vs placebo: An analysis of mode of radiographic progression in COU-AA-302

Benjamin A. Teply, Fang Qiu, Emmanuel S. Antonarakis, Michael A. Carducci, Samuel R. Denmeade

Research output: Contribution to journalArticle

Abstract

Background: Abiraterone increases survival in prostate cancer, but tumors resistant to abiraterone can exhibit a hormonally resistant, aggressive phenotype. We hypothesized that the therapeutic pressure of abiraterone is resulting in more clinically aggressive disease at progression, characterized by increased visceral metastases. Our objective was to determine whether abiraterone increased the risk of development of visceral metastases at the time of progression compared with placebo in a randomized phase III trial. Methods: We performed a post hoc analysis of the COU-AA-302 trial of abiraterone plus prednisone vs placebo plus prednisone in patients with metastatic castration-resistant prostate cancer. The primary outcome was the development of visceral metastases. The cumulative incidences of visceral metastases were calculated by the Kaplan-Meier method and compared using log-rank testing. Multivariable Cox regression analysis assessed for the independent association of abiraterone with the development of visceral metastases. Results: Eighty-four of 1088 patients developed visceral metastases during study. Log-rank testing and Cox regression showed no difference in time to visceral metastases between groups (HR 1.01 [95% confidence interval (CI), 0.65-1.56]; P =.97). Abiraterone treatment was not associated with the development of visceral metastases in multivariable analysis (HR 0.89 [95% CI, 0.57-1.40]; P =.62). The study was limited by censoring of radiographic outcomes at the time of completion of primary study therapy; longer term risks were not assessed. Conclusions: Abiraterone was not associated with increased risk of visceral metastatic disease at the time of progression compared with placebo.

Original languageEnglish (US)
Pages (from-to)929-933
Number of pages5
JournalProstate
Volume79
Issue number8
DOIs
StatePublished - Jun 1 2019

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Placebos
Neoplasm Metastasis
Prednisone
Prostatic Neoplasms
Confidence Intervals
abiraterone
Castration
Disease Progression
Therapeutics
Regression Analysis
Phenotype
Pressure
Survival
Incidence
Neoplasms

Keywords

  • abiraterone
  • metastatic castration-resistant prostate cancer
  • visceral liver metastases

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Risk of development of visceral metastases subsequent to abiraterone vs placebo : An analysis of mode of radiographic progression in COU-AA-302. / Teply, Benjamin A.; Qiu, Fang; Antonarakis, Emmanuel S.; Carducci, Michael A.; Denmeade, Samuel R.

In: Prostate, Vol. 79, No. 8, 01.06.2019, p. 929-933.

Research output: Contribution to journalArticle

Teply, Benjamin A. ; Qiu, Fang ; Antonarakis, Emmanuel S. ; Carducci, Michael A. ; Denmeade, Samuel R. / Risk of development of visceral metastases subsequent to abiraterone vs placebo : An analysis of mode of radiographic progression in COU-AA-302. In: Prostate. 2019 ; Vol. 79, No. 8. pp. 929-933.
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abstract = "Background: Abiraterone increases survival in prostate cancer, but tumors resistant to abiraterone can exhibit a hormonally resistant, aggressive phenotype. We hypothesized that the therapeutic pressure of abiraterone is resulting in more clinically aggressive disease at progression, characterized by increased visceral metastases. Our objective was to determine whether abiraterone increased the risk of development of visceral metastases at the time of progression compared with placebo in a randomized phase III trial. Methods: We performed a post hoc analysis of the COU-AA-302 trial of abiraterone plus prednisone vs placebo plus prednisone in patients with metastatic castration-resistant prostate cancer. The primary outcome was the development of visceral metastases. The cumulative incidences of visceral metastases were calculated by the Kaplan-Meier method and compared using log-rank testing. Multivariable Cox regression analysis assessed for the independent association of abiraterone with the development of visceral metastases. Results: Eighty-four of 1088 patients developed visceral metastases during study. Log-rank testing and Cox regression showed no difference in time to visceral metastases between groups (HR 1.01 [95{\%} confidence interval (CI), 0.65-1.56]; P =.97). Abiraterone treatment was not associated with the development of visceral metastases in multivariable analysis (HR 0.89 [95{\%} CI, 0.57-1.40]; P =.62). The study was limited by censoring of radiographic outcomes at the time of completion of primary study therapy; longer term risks were not assessed. Conclusions: Abiraterone was not associated with increased risk of visceral metastatic disease at the time of progression compared with placebo.",
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T2 - An analysis of mode of radiographic progression in COU-AA-302

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AU - Qiu, Fang

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AU - Carducci, Michael A.

AU - Denmeade, Samuel R.

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N2 - Background: Abiraterone increases survival in prostate cancer, but tumors resistant to abiraterone can exhibit a hormonally resistant, aggressive phenotype. We hypothesized that the therapeutic pressure of abiraterone is resulting in more clinically aggressive disease at progression, characterized by increased visceral metastases. Our objective was to determine whether abiraterone increased the risk of development of visceral metastases at the time of progression compared with placebo in a randomized phase III trial. Methods: We performed a post hoc analysis of the COU-AA-302 trial of abiraterone plus prednisone vs placebo plus prednisone in patients with metastatic castration-resistant prostate cancer. The primary outcome was the development of visceral metastases. The cumulative incidences of visceral metastases were calculated by the Kaplan-Meier method and compared using log-rank testing. Multivariable Cox regression analysis assessed for the independent association of abiraterone with the development of visceral metastases. Results: Eighty-four of 1088 patients developed visceral metastases during study. Log-rank testing and Cox regression showed no difference in time to visceral metastases between groups (HR 1.01 [95% confidence interval (CI), 0.65-1.56]; P =.97). Abiraterone treatment was not associated with the development of visceral metastases in multivariable analysis (HR 0.89 [95% CI, 0.57-1.40]; P =.62). The study was limited by censoring of radiographic outcomes at the time of completion of primary study therapy; longer term risks were not assessed. Conclusions: Abiraterone was not associated with increased risk of visceral metastatic disease at the time of progression compared with placebo.

AB - Background: Abiraterone increases survival in prostate cancer, but tumors resistant to abiraterone can exhibit a hormonally resistant, aggressive phenotype. We hypothesized that the therapeutic pressure of abiraterone is resulting in more clinically aggressive disease at progression, characterized by increased visceral metastases. Our objective was to determine whether abiraterone increased the risk of development of visceral metastases at the time of progression compared with placebo in a randomized phase III trial. Methods: We performed a post hoc analysis of the COU-AA-302 trial of abiraterone plus prednisone vs placebo plus prednisone in patients with metastatic castration-resistant prostate cancer. The primary outcome was the development of visceral metastases. The cumulative incidences of visceral metastases were calculated by the Kaplan-Meier method and compared using log-rank testing. Multivariable Cox regression analysis assessed for the independent association of abiraterone with the development of visceral metastases. Results: Eighty-four of 1088 patients developed visceral metastases during study. Log-rank testing and Cox regression showed no difference in time to visceral metastases between groups (HR 1.01 [95% confidence interval (CI), 0.65-1.56]; P =.97). Abiraterone treatment was not associated with the development of visceral metastases in multivariable analysis (HR 0.89 [95% CI, 0.57-1.40]; P =.62). The study was limited by censoring of radiographic outcomes at the time of completion of primary study therapy; longer term risks were not assessed. Conclusions: Abiraterone was not associated with increased risk of visceral metastatic disease at the time of progression compared with placebo.

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