Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel

Avivit Peer, Maya Gottfried, Victoria Sinibaldi, Michael A Carducci, Mario Eisenberger, Avishay Sella, Raya Leibowitz-Amit, Raanan Berger, Daniel Keizman

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC. METHODS: Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n=140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. RESULTS: The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P=0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P=0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P=0.043), median OS 19 versus 11 months (HR 0.53, P=0.79), and treatment interruption d/t severe adverse events 8% (n=2) versus 31% (n=8) (0R 0.6, P=0.023). CONCLUSIONS: In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole. Prostate 74:433-440, 2014.

Original languageEnglish (US)
Pages (from-to)433-440
Number of pages8
JournalProstate
Volume74
Issue number4
DOIs
StatePublished - 2014

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docetaxel
Ketoconazole
Castration
Prostatic Neoplasms
Disease-Free Survival
Survival
Databases
Neoplasm Grading
Therapeutics
Abiraterone Acetate
abiraterone
Prostate
Research Design

Keywords

  • Abiraterone
  • Ketoconazole
  • Metastatic castration resistant and docetaxel refractory prostate cancer
  • Outcome

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel. / Peer, Avivit; Gottfried, Maya; Sinibaldi, Victoria; Carducci, Michael A; Eisenberger, Mario; Sella, Avishay; Leibowitz-Amit, Raya; Berger, Raanan; Keizman, Daniel.

In: Prostate, Vol. 74, No. 4, 2014, p. 433-440.

Research output: Contribution to journalArticle

Peer, Avivit ; Gottfried, Maya ; Sinibaldi, Victoria ; Carducci, Michael A ; Eisenberger, Mario ; Sella, Avishay ; Leibowitz-Amit, Raya ; Berger, Raanan ; Keizman, Daniel. / Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel. In: Prostate. 2014 ; Vol. 74, No. 4. pp. 433-440.
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T1 - Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel

AU - Peer, Avivit

AU - Gottfried, Maya

AU - Sinibaldi, Victoria

AU - Carducci, Michael A

AU - Eisenberger, Mario

AU - Sella, Avishay

AU - Leibowitz-Amit, Raya

AU - Berger, Raanan

AU - Keizman, Daniel

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC. METHODS: Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n=140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. RESULTS: The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P=0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P=0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P=0.043), median OS 19 versus 11 months (HR 0.53, P=0.79), and treatment interruption d/t severe adverse events 8% (n=2) versus 31% (n=8) (0R 0.6, P=0.023). CONCLUSIONS: In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole. Prostate 74:433-440, 2014.

AB - BACKGROUND: Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC. METHODS: Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n=140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. RESULTS: The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P=0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P=0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P=0.043), median OS 19 versus 11 months (HR 0.53, P=0.79), and treatment interruption d/t severe adverse events 8% (n=2) versus 31% (n=8) (0R 0.6, P=0.023). CONCLUSIONS: In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole. Prostate 74:433-440, 2014.

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KW - Outcome

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