Androgen dynamics and serum PSA in patients treated with abiraterone acetate

C. J. Ryan, W. Peng, T. Kheoh, E. Welkowsky, C. M. Haqq, D. W. Chandler, H. I. Scher, A. Molina

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38). The association between PSA response (≤50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression. Results: A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P≤0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546-4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels. Conclusions: Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.

Original languageEnglish (US)
Pages (from-to)192-198
Number of pages7
JournalProstate Cancer and Prostatic Diseases
Volume17
Issue number2
DOIs
StatePublished - Jun 2014
Externally publishedYes

Bibliographical note

Funding Information:
C J Ryan has received honoraria from Janssen Pharmaceuticals. W Peng is an employee of Janssen Research & Development. T Kheoh and A Molina are employees of Janssen Research & Development and own stock in Johnson & Johnson. C M Haqq owns stock in Johnson & Johnson. D W Chandler is an employee of LabCorp and owns stock in LabCorp. H I Scher has served as a consultant (uncompensated) for Aragon Pharmaceuticals, Celgene, Orion Pharmaceuticals, Johnson & Johnson Pharmaceutical Development, Medivation and Veridex (now Janssen Research & Development); is a consultant (compensated) for Enzon, Millennium and Ortho Biotech Oncology Research and Development; and has received institutional support for research funding from Aragon Pharmaceuticals, Janssen Research & Development, Medivation and Veridex (now Janssen Research & Development). E Welkowsky declares no conflict of interest.

Funding Information:
This study was funded by Ortho Biotech Oncology Research & Development unit of Cougar Biotechnology (now Janssen Research & Development). We are grateful to Russell P Grant, PhD, of Endocrine Sciences, a Laboratory Corporation of America Company (Calabasas Hills, CA, USA) for his role in the development and validation of the androgen assay that led to its inclusion in this study, and for his critical review of this manuscript. Writing assistance was provided by Ira Mills, PhD, of PAREXEL, and was funded by Janssen Global Services, LLC.

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