Experimental drug – Enzalutamide – moderately increases survival in patients with advanced prostate cancer

This clinical trial evaluated the survival benefits of a drug named Enzalutamide (Xtandi) for patients with non-responsive (refractory) advanced prostate cancer previously treated with chemotherapy. Main findings: Enzalutamide prolonged survival by approximately 5 months and reduced the risk of death by 37%.

The majority of prostate cancers are hormone-dependent. Reducing the level of androgens by surgical or medical means slows down the progression of the disease. Advanced metastatic tumors, however, often cease to respond to hormone-reducing treatments, thereafter termed ‘castration-resistant’. These tumor cells have very high levels of androgen receptors (proteins that mediate the cancer cell response to male sex hormones). As a result, they continue growing even when the level of hormones in the body is very low. Enzalutamide targets androgen receptors and prevents them from binding to hormone molecules, thus potentially reducing the growth rate of cancer.

The trial included 1199 men with castration-resistant prostate cancer, with prior chemotherapy treatments. 800 men received Enzalutamide and 399 were given placebo (a drug with no biological activity).

Enzalutamide prolonged survival from 13.6 to 18.6 months, compared with placebo. It was also superior to placebo in decreasing the levels of  Prostate-Specific Antigen (PSA; a diagnostic marker whose level reflects the progression of the disease), improving progression-free survival (men living without evidence of any progression of the disease in CT/PET scans), delaying the development of bone metastases and other complications, and improving the quality-of-life scores (measured using a questionnaire). The average time to any significant adverse event was 3 times longer (12.6 vs. 4.2 months) in the treatment group comparing to placebo. However, side effects such as fatigue, diarrhea, and hot flashes were more common in the Enzalutamide group. Seizures were reported in five patients (0.6%) receiving Enzalutamide.

In summary, Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. It could therefore be considered as a treatment option for such patients.

This study was limited to investigating the effect of Enzalutamide in men with metastatic aggressive forms of cancer only. No clear data is yet available for patients who didn’t receive prior chemotherapy or for earlier stages of cancer (trials are ongoing).

The study was funded by Funded by Medivation and Astellas Pharma Global Development, the manufacturers of Enzalutamide.