Abiraterone Acetate (Zytiga) and enzalutamide (Xtandi) are the newest generation hormonal agents.  They both have demonstrated a survival advantage in men with castrate resistant prostate cancer (CRPC) who have already been treated with docetaxel (chemotherapy). Unfortunately all men who are responsive to both of these drugs eventually become resistant.   Some men are subject to early progression (failure) within the first 3 months of the treatment.  This leads to an early treatment interruption.

In an analysis of the situation researchers have tried to identify which factor, if any, may predict this early failure of either of these drugs.

The researchers evaluated a consecutive series of 57 men (a small sample) treated between September 2011 and March 2013 . Twenty-six men received Zytiga  (1,000 mg po + prednisone 10 mg po daily) and 31 Xtandi (160 mg po daily).

Pre and post treatment clinical history, the treatment details and outcomes where all recorded. They evaluated a series of 24 selected clinical factors to predict early drug failure.

Among the 24 factors that were evaluated the presence of pain at baseline, high baseline lactate dehydrogenase levels and PSA levels after one month of treatment were predictive of early failure. However only the PSA levels at 1 month were confirmed at the multivariate analysis as a possible biomarker.  Men failing to achieve a 50% or more PSA reduction, compared to baseline were more likely to experience an early failure (48% vs 15%). Moreover, a clear difference in both progression free survival (PFS) and overall survival

[median 17 vs 7 mos ( p = 0.0009)] was observed between men who achieved at least a 50% PSA reduction at 1-month.

The researchers concluded that their results seem to suggest that PSA trend may represent a simple and rapid method of identifying men who will have an early failure of Zytiga and Xtandi.  Men failing to achieve at least a 50% reduction within the first month of treatment should received a more intensive monitoring. These data need to be confirmed in a larger patient population.

J Clin Oncol 32, 2014 (suppl; abstr e16044); Antonello Veccia, Orazio Caffo, Francesca Maines, Alberto Bonetta, Gilbert Spizzo, Enzo Galligioni

Joel T. Nowa, M.A., M.S.W.k