(ChemotherapyAdvisor) – Serum androgens appear to be prognostic of overall survival (OS) among men with castration-resistant prostate cancer (CRPC), according to a post-hoc analysis of data from the randomized phase 3 COU-AA-301 clinical study, presented at the 2013 Genitourinary Cancers Symposium in Orlando, FL.

“Median OS increased in a step-wise fashion per T quartile, regardless of treatment (P<0.0001),” reported lead author Charles J. Ryan, MD, at the University of California, San Francisco, San Francisco, CA, and coauthors.Baseline serum androgen concentrations as measured by an ultrasensitive mass spectrometric assay may be prognostic of OS in mCRPC patients” and deserve consideration as a stratification variable in phase 3 trials, they concluded[NR1] .

Reported median OS for testosterone quartiles were: Q1 (T ≤2.3 ng/dL): 10.4 (8.8-11.6); Q2 (T ≤5 ng/dL): 13.3 (11.2-14.9); Q3 (T≤8.6 ng/dL): 16.1 (14.8-18.0); and Q4 (T>8.6 ng/dL): 18.9 (16.9, NE), the authors reported[NR2] .

“Serum testosterone (T) and precursors, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A4), may be prognostic of overall survival (OS) by identifying patients with varying dependency on androgen,” Dr. Ryan and his coauthors noted[NR3] .


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To determine if this is the case, the authors studied associations between OS and the distribution of serum androgen concentrations among patients with mCRPC treated in the COU-AA-301 study of abiraterone acetate (AA; 1,000 mg) plus prednisone (P) versus P alone. Serum androgen concentrations were measured using ultrasensitive mass spectrometric assays, the authors reported[NR4] .

“T, DHEAS, and A4 serum levels were measured using novel liquid-liquid extraction 1D or 2D-LC/tandem mass spectrometry ((LC)-LC-MS/MS) assays,” they explained[NR5] .

Patients with baseline T at 50 ng/dL or higher were stratified by Eastern Cooperative Oncology Group performance status (0-1 vs. 2), pain (present vs. absent), the number of prior chemotherapy regimens administered (one vs. two), and type of progression (prostate-specific antigen only vs. radiographic), the coauthors reported. Baseline androgen levels (testosterone, androstenedione, DHEAS) “as measured by the ultrasensitive assays, were available for 768 (97%), 752 (95%), and 781 (99%) patients, respectively, in the AA arm, and 383 (97%), 366 (93%), and 387 (98%) patients, respectively, in the P arm,” Dr. Ryan told ChemotherapyAdvisor.com[NR6] .

A positive association was observed in the multivariate analysis adjusted for treatment, other androgens, and lab parameters (LDH, HGB, ALKP, PSA; all Ps<0.0001),” they reported. “In AA and P-treated patients, respectively, the hazard ratio for OS (95% CI) comparing patients with baseline T above and below baseline median was 0.64 (0.53-0.77; P<0.0001) and 0.51 (0.39-0.67; P=0.0004[NR7] ).” 

The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).

Clinical trial information: NCT00638690

Abstract [http://gucasym.asco.org/content/107123-134]


 [NR1]Confirmed.

 [NR2]Confirmed.

 [NR3]Confirmed.

 [NR4]Confirmed.

 [NR5]Confirmed.

 [NR6]Confirmed via interview.

 [NR7]Confirmed.