Medivation Inc. and Astellas Pharma Inc. have announced final results on the primary and secondary efficacy endpoints from the Phase 3 PREVAIL trial of enzalutamide in patients with chemotherapy-naïve metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms. Data will be shared in a late-breaking oral presentation at the upcoming American Society of Clinical Oncology (ASCO) 2014 Genitourinary (GU) Cancers Symposium in San Francisco on Thursday, January 30, 2014.[i] http://spoor.co.uk/blog/show/blogid/113213/id/47657
"This is a significant step forward in prostate cancer therapy for men whose cancer has progressed, despite treatment with androgen deprivation therapy" said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. "As well as the clear efficacy benefits, what impressed me most about the results is that treatment with enzalutamide delays the time to initiation of chemotherapy, a key factor in maintaining quality of life in men with advanced prostate cancer."
The PREVAIL study results in men with metastatic prostate cancer who have progressed on androgen deprivation therapy are as follows:
Treatment with enzalutamide demonstrated a statistically significant overall survival benefit compared with placebo treatment. Enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.0001), compared with placebo. This benefit was observed despite substantial use of subsequent therapies (40% in the enzalutamide and 70% in the placebo groups).[i]
Treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19; p<0.0001).[i]
Consistent benefits on these co-primary endpoints of overall survival and radiographic progression-free survival were observed across patient subgroups.[i]
Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001).[i]
The majority of men (58.8%) with soft tissue metastatic disease treated with enzalutamide versus 5% of patients treated with placebo had objective responses (complete responses or partial responses) including complete responses in 19.7% of enzalutamide patients compared with 1% of placebo patients.[i]
Enzalutamide extended the median time to PSA progression from 2.8 months (placebo) to 11.2 months (HR=0.169; p<0.0001).[ii]
Nearly 4 out of 5 patients in the enzalutamide group experienced a PSA decline of 50% or more, compared to less than 4% in the placebo group (78% vs. 3.5%; p<0.0001).[ii]
The median times to deterioration in a measure of prostate cancer-specific quality of life, the Functional Assessment of Cancer Therapy-Prostate or FACT-P, were 11.3 months for the enzalutamide-treated patients and 5.6 months for the placebo patients (HR= 0.625, p<0.0001).[ii]
The median treatment duration for enzalutamide was more than 3 times longer than for placebo (16.6 versus 4.6 months).[ii]
Common side effects occurring during treatment and more common in the enzalutamide treated men included fatigue, back pain, constipation and arthralgia. Hypertension was observed in 13.4% of enzalutamide versus 4.1% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 2.8% of enzalutamide versus 2.1% of placebo-treated patients. Investigators reported zero seizures in the enzalutamide-treated group and one in the placebo group prior to the data cut-off date. One seizure was reported in the enzalutamide group after the data cut-off date.[i]
"Medivation's primary mission is to develop and make available to patients medically innovative therapies that provide clinically meaningful benefits and address major medical unmet needs among a spectrum of serious diseases," said David Hung, M.D., founder, president and CEO of Medivation. "Should enzalutamide be approved for use in this patient population, it will be a meaningful advance in the field of prostate cancer therapy."