Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer

G. Sonpavde, G. R. Pond, A. J. Templeton, Eugene D Kwon, J. S. de Bono

Research output: Contribution to journalArticle

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Abstract

Background:Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities.Methods:Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided.Results:Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72–1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ⩾1, Gleason score ⩾8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ⩾3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03–2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ECOG-PS ⩾1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration.Conclusions:P plus placebo was associated with higher grade ⩾3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance.Prostate Cancer and Prostatic Diseases advance online publication, 27 September 2016; doi:10.1038/pcan.2016.44.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StateAccepted/In press - Sep 27 2016

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Castration
Prednisone
Prostatic Neoplasms
Placebos
docetaxel
Survival
Hypoalbuminemia
L-Lactate Dehydrogenase
Prostatic Diseases
Confidence Intervals
Asthenia
Neoplasm Grading
Anorexia
Proportional Hazards Models
Fatigue
Publications
Neoplasm Metastasis
Pain
Liver

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

Cite this

Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer. / Sonpavde, G.; Pond, G. R.; Templeton, A. J.; Kwon, Eugene D; de Bono, J. S.

In: Prostate Cancer and Prostatic Diseases, 27.09.2016.

Research output: Contribution to journalArticle

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title = "Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer",
abstract = "Background:Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities.Methods:Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided.Results:Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95{\%} confidence interval 0.72–1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ⩾1, Gleason score ⩾8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ⩾3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95{\%} confidence interval 1.03–2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ECOG-PS ⩾1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration.Conclusions:P plus placebo was associated with higher grade ⩾3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance.Prostate Cancer and Prostatic Diseases advance online publication, 27 September 2016; doi:10.1038/pcan.2016.44.",
author = "G. Sonpavde and Pond, {G. R.} and Templeton, {A. J.} and Kwon, {Eugene D} and {de Bono}, {J. S.}",
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T1 - Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer

AU - Sonpavde, G.

AU - Pond, G. R.

AU - Templeton, A. J.

AU - Kwon, Eugene D

AU - de Bono, J. S.

PY - 2016/9/27

Y1 - 2016/9/27

N2 - Background:Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities.Methods:Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided.Results:Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72–1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ⩾1, Gleason score ⩾8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ⩾3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03–2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ECOG-PS ⩾1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration.Conclusions:P plus placebo was associated with higher grade ⩾3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance.Prostate Cancer and Prostatic Diseases advance online publication, 27 September 2016; doi:10.1038/pcan.2016.44.

AB - Background:Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities.Methods:Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided.Results:Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72–1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ⩾1, Gleason score ⩾8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ⩾3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03–2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ECOG-PS ⩾1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration.Conclusions:P plus placebo was associated with higher grade ⩾3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance.Prostate Cancer and Prostatic Diseases advance online publication, 27 September 2016; doi:10.1038/pcan.2016.44.

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