Elevated pretreatment androgen levels correlate with significantly better overall survival in men with castration-resistant prostate cancer, regardless of treatment, a recent post hoc analysis of a large randomized trial showed.
Whether men were allocated to placebo or the androgen synthesis inhibitor abiraterone acetate (ZYTIGA), those with higher baseline levels of adrenal androgens had a 33% improvement in overall survival. Higher androgen levels in placebo-treated patients also correlated with improved survival, according to a presentation at the American Association for Cancer Research annual meeting in Chicago.
"Baseline androgen levels were both prognostic and predictive of overall survival," said first author Charles J. Ryan, MD, associate professor of medicine and urology at the University of California, San Francisco. "They were prognostic because high baseline adrenal androgens were associated with a survival advantage over low baseline levels, independent of therapy. They were predictive in that, among abiraterone-treated patients, higher baseline androgen levels were predictive of improved survival overall."
The COU-AA-301 trial involved 1,195 men with CRPC who were randomized 2:1 to abiraterone or placebo. Men in both groups received prednisone.
For purposes of the post hoc analysis, the authors defined androgen levels according to median values. Levels that exceeded the median were considered high.
Supramedian adrenal androgen values were associated with improved overall survival. The association held true for testosterone, androstenedione, and DHEA. The magnitude of the difference in survival in men with high versus low androgen levels ranged between 32% and 36% for abiraterone (p<.0001 for all comparisons) and between 38% and 49% in the placebo group (p=.0004 to p=.0002).
"Patients treated with prednisone alone showed longer overall survival with high hormone levels," said Dr. Ryan. "That does suggest-but does not prove-that prednisone modulates the adrenal axis."
20% improvement in survival
Comparison of the two treatment groups showed that abiraterone-treated patients had improved survival among men with high or low baseline androgen levels. Abiraterone was associated with about a 20% improvement in survival among men with high baseline androgens, but only the difference in DHEA reached statistical significance (HR 0.78, p=.0343). Among men with low baseline androgen levels, the abiraterone survival benefit versus placebo was about 30% for each of the androgens (p=.00019 to p=.0003).
Men with high or low baseline androgen levels lived longer when treated with abiraterone. Among high-androgen men, median overall survival approached 18 months with abiraterone versus 15 to 16 months with placebo. Men with low androgen levels had a median overall survival of about 14 months with abiraterone versus 10 months with placebo.
High baseline androgen levels remained significantly associated with improved survival after adjustment for treatment, other androgens, and other laboratory parameters. Analysis of response rates showed a similar relationship, as patients with higher baseline androgen values had improved odds for response.
Dr. Ryan has received research support from Cougar Biotechnology and Amgen, and his co-authors have a financial or other relationship with Johnson & Johnson and/or Janssen Biotech (formerly Ortho Biotech). The study was sponsored by Cougar Biotechnology.