What will happen when enzalutamide (Xtandi) is approved for use in advanced prostate cancer in the disease stage prior to chemotherapy (that is if it is approved)?  Already occupying this space and already approved by the FDA is both Provenge and abiraterone (Zytiga).  Where will Xtandi fit in?

Until we have a lot more data, which will inform our doctors, we can only guess what the optimum treatment sequence should be to provide the longest survival opportunity.  So, here is my guess and my rational for my guess.

The first FDA approved treatment used should be Provenge (although I personally would participate in the ProstVac trial before moving to Provenge, but I would move to Provenge the day I completed the trial).  Provenge takes time to work and will be most effective while the PSA is low.  The lower the better, so Provenge should be the first treatment used when a man becomes castrate resistant.

After completing the three Provenge infusions doctors will be faced with a decision to use either Xtandi or Zytiga.  We do know that both drugs do cause some degree of cross-resistance to the other; this needs to be weighed in the decision process.  Xtandi is more expensive than Zytiga.   So, which drug t o use?

My vote is for Xtandi, despite its higher cost.  Xtandi does not require the simultaneous use of a steroid while Zytiga does require a steroid.  More importantly, in the Phase 3 trial of Xtandi, Xtandi had a 29% reduction of risk of death compared to 21% for Zytiga. Better survival possibilities equal a better treatment when all other factors are equal.

All of this discussion doesn’t take into the possibility of  combining both Zytiga and Xtandi as a better treatment option.

Could I be wrong, of course I might not be correct.  It is possible that the insurance companies aggressive moves to Step Therapy will force doctors to use the less expensive drug Zytiga first, but I don’t believe that this is the best direction for us men with advanced prostate cancer.

Joel T. Nowak, M.A., M.S.W.