The makers of Enzalutamide (Xtandi), Astellas Pharma US, Inc and Medivation, Inc have begun a Phase 4 clinical trial known as PLATO. The study is designed to evaluate the efficacy and safety of continued treatment with enzalutamide (Xtandi) plus abiraterone acetate (Zytiga) and prednisone as compared to treatment with Zytiga and prednisone alone in men who have not yet had chemotherapy treatment for advanced prostate cancer that has advanced following failed therapy with Xtandi.

This trial will be global; randomized; double blind; placebo-controlled and scheduled to enroll approximately 500 chemotherapy-naive men. All subjects will initially receive treatment with Xtandi. Those men who experience disease progression on Xtandi will be randomized to treatment with Xtandi plus Zytiga and prednisone or to Zytiga and prednisone. The primary endpoint of the trial is progression-free survival.

The trial will evaluate Xtandi at a dose of 160 mg taken orally once daily in combination with Zytiga at a dose of 1000 mg administered orally once daily and prednisone at a dose of 5 mg administered orally twice daily, versus placebo plus the same doses of Zytiga and prednisone.

Xtandi is FDA approved only in the post-chemotherapy stage and not yet approved for use in men who have not yet had chemotherapy. Zytiga with prednisone is approved for use both in the pre-chemotherapy and post-chemotherapy stage of treatment of advanced prostate cancer. Despite this there have been a number of men who have had Xtandi prior to chemotherapy. In an attempt to move Xtandi formally into the pre-chemotherapy sequence there was a phase 3 clinical trial which was halted early due to very strong and positive data (we anticipate FDA approval in 2014).

This phase 4 trial is most interesting given the issues around step therapy that has led to many insurance companies refusing to pay for Xtandi until Zytiga has failed (see my many recent posts about this issue by searching for “step therapy” and “fail first “ therapy on this blog). The pharmaceutical companies are clearly trying to place Xtandi back in the running as a first line drug prior to Zytiga in the pre-chemotherapy stage. The very positive result for us survivors is that we will get some clinical data that might influence us in the use of these two great drugs in combination (the beginning of the elusive cocktail I have written about) as well as possible ending the step therapy practice. However, I do believe that the pharmaceuticals are making an error and letting us down by not designing this phase 4 trial to have survival as a primary endpoint (the end point is disease progression).

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