Which Drug First - Zytiga or Xtandi?

One of the most puzzling questions faced by men with advanced prostate cancer has to do with deciding which drug to take first, Zytiga (abiraterone) or Xtandi (enzalutamide)?  It is confusing because both are FDA approved for men who are chemotherapy-naïve with metastatic castrate resistant prostate cancer (mCRPC).


Zytiga and Xtandi have not been evaluated with a head to head clinical trial, which is the only valid method, to know if there is a difference.  The current best information we have comes from a retrospective study (Terada) evaluating 198 men from Kyoto University Hospital in Kyoto, Japan and the Johns Hopkins Cancer Center in Baltimore, MD. 

The study compared both progression-free survival and overall survival (OS) for men who took Zytiga then moved on at disease progression to Xtandi to a group of men who started with Xtandi then, on disease progression moved on to Zytiga. 

They concluded that taking Zytiga first had a slight advantage over taking Xtandi as the first of the two treatments.  This conclusion was not statistically significant and did not take into account the differences in the prostate cancer that do exist from one man to another.

Despite the study’s finding, which was indeterminate, in our opinion, the question remains unresolved.  Until we do have data from a direct, head-to-head evaluation that is designed to be sensitive to genetic differences in the prostate cancer we cannot say which treatment should precede the other, despite the data from the Terada study.