Today we have two different drugs which may be used in the first line for castration-resistant prostate cancer – enzalutamide and docetaxel. According to the different mechanisms of action of these two different agents, there is a strong rationale for the combination of these agents in the first line. So we planned to perform a phase II randomised trial comparing docetaxel alone at the standard dose of 75mg/m2 for eight doses plus prednisone 5mg bis in die (BID) and androgen deprivation therapy and the same treatment plus enzalutamide to the standard dose of 160mg daily for 24 weeks.

This is a phase II randomised trial and the main endpoint is the rate of patients without progressive disease at the end of the treatment. We have other several secondary endpoints such as radiological progression-free survival, progression-free survival, overall survival, safety, quality of life, pain, objective response rate and biochemical response rate.

The treatment was well tolerated; grade 3/4 neutropenia and febrile neutropenia, skin toxicities and fatigue were more frequently observed in the combination arm compared to the standard arm. The trial was positive since it met its primary endpoint since the rate of patients without progression was 89% in the combination arm and 73% in the docetaxel alone arm. This difference was statistically significant with a relative improvement of the possibility of response in about 16% and the number needed to treat of 6.19.

Also the median progression-free survival was in favour of the combination arm. The median progression-free survival of the combination arm was 10.1 months compared to 9.1 months in the standard arm. The difference was statistically significant with a reduction of risk of progression of 29%. We did not find any statistically significant difference in terms of overall survival.

So, in conclusion, our study was the first phase II randomised trial comparing the standard treatment to the combination of docetaxel plus enzalutamide, confirmed the efficacy of this combination which demonstrated to be safe and feasible.

It’s very difficult today in the actual landscape of prostate cancer to perform a phase III trial because the natural next step should be the development of a phase III trial but it’s very difficult because in this moment all the new drugs, all the new agents, are more devoted in the early phases of the disease, in the castration sensitive phase, in the M0 or M1 castration sensitive phase, so it’s very difficult to perform a phase III trial. But this trial provided a strong rationale for combining chemotherapy and new androgen receptor targeting agents.