Baseline serum androgen levels and responses to abiraterone acetate

Baseline levels of serum androgens were predictive for clinical response to treatment in the Phase III clinical trial of abiraterone acetate in men with chemotherapy-refractory, metastatic, castration-resistant prostate cancer (mCRPC), according to a new article in the Journal of Clinical Oncology.

This newly published paper by Ryan et al. used data collected during the COU-AA-301 study of abiraterone acetate + prednisone compared to prednisone alone in men with mCRPC who were progressing after docetaxel-basec chemotherapy. The authors report on the use of an ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography method, coupled to mass spectrometry, to measure levels of serum androgens (including testosterone, androstenedione, and dehydroepiandrosterone sulphate). They then used the available data to correlate serum androgen levels over time to the patients’ overall survival.
Here are the basic results of the study:

  • Median overall survival increased with each quartile increase in serum testosterone level — regardless of treatment arm.
  • Serum androgen levels at baseline were strongly associated with survival (P < 0.0001) in bivariate and multivariable analyses.
  • Longer survival was observed among those men with baseline serum androgen levels above as opposed to below the median in the abiraterone + prednisone and in the prednisone alone arms of the trial.
    • As an example, based on serum testosterone levels in the abiraterone + prednisone arm of the trial, the hazard ratio (HR) was 0.64 (P < 0.0001).
  • Treatment with abiraterone + prednisone led to longer survival compared to prednisone alone alone in the above-median and the below-median groups for all androgens.

The authors conclude that baseline serum androgen levels measured using an ultrasensitive assay were prognostic for overall survival in this trial and may be useful for risk stratification in future clinical trials of men with mCRPC.

To explain this finding in “English” (so to speak), what the authors have been able to show is that men with higher serum androgen levels at start of therapy had better responses to treatment with abiraterone acetate + prednisone and with prednisone alone. Since both of these types of therapy are known to lower serum androgen levels in men with mCRPC, it makes sense that men who start with higher levels of serum androgens may get a better response to these types of therapy than the men with lower baseline serum androgen levels.

It will be interesting to see whether similar data can be made available from the comparable trial of enzalutamide in men with chenotherapy-refractory mCRPC.

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