We have made major progress by moving docetaxel forward, and now the largest pool of patients who become hormone resistant have received local therapy and then progressed. We have a lot of drugs for castration-resistant prostate cancer, and we are studying them earlier in the course of disease, but we have created a lot of confusion and don’t really know the best way to use them,” said formal discussant Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Associate Professor of Physiology at Université Catholique de Louvain, Brussels.

“Regarding the orteronel study, results show maintenance therapy has the potential to delay progression. Unfortunately, the drug has been abandoned. The study shows that maintenance is feasible but not better. Clearly, we have to move forward,” said Dr. Tombal.

Turning to the enzalutamide study, he said, “We don’t have the ability to eradicate micrometastasis. Three drugs appear to be better than one, but only in a subset of patients. Enzalutamide alone is weaker than the three-drug arm, but it may be enough for selected patients. It is worth investigating enzalutamide/dutasteride to act on the testosterone surge seen with GnRH agonists.”

Dr. Tombal was encouraged by the TAK-385 results. “On paper, at the end of phase II, TAK-385 appears to be an extremely attractive way to overcome disadvantages of degarelix [Firmagon; another GnRH antagonist that has been studied]. The drug is promising.” Dr. Tombal continued: “We need to know long-term genitourinary tolerance and adherence. TAK-385 appears to solve most of the problems with depot GnRH agonists. The question is if antagonists had been developed first, would we have ever used an agonist?”   ■

Disclosure: Dr. Tombal is a paid advisor or investigator for Amgen, Astellas, Bayer, Medivation, Ferring Pharmaceuticals, Janssen, and Sanofi-Aventis.