MedWire News: Enzalutamide treatment significantly improves survival in men with castration-resistant prostate cancer, demonstrate phase III trial results published in TheNew England Journal of Medicine.
Men randomly assigned to receive the androgen receptor-signaling inhibitor after chemotherapy had a median overall survival of 18.4 months compared with just 13.6 months for placebo-treated patients.
Multivariate analysis showed that this survival benefit occurred in patients after adjustment for baseline characteristics, regardless of whether they were stratified by age and Eastern Cooperative Oncology Group (ECOG) status, geographic location, disease extent by imaging, and biochemical factors including prostate-specific antigen, report Howard Scher (Memorial Sloan-Kettering Cancer Center, New York, USA) and co-authors.
"These results validate androgen-receptor signaling as a key therapeutic target throughout the clinical spectrum of prostate cancer, including in men who have received previous chemotherapy," they say.
The study, which included 1199 men treated with enzalutamide 160 mg/day (n=800) or placebo (n=399), was halted after planned interim analysis after 520 deaths showed a hazard ratio for overall survival of 0.63. The patient groups had received a median of 8.3 and 3.0 months' treatment, respectively.
Enzalutamide was also shown to be significantly better than placebo for all secondary endpoints: reduction of PSA level by 50% or more (54 vs 2%); soft tissue response (29 vs 4%); quality of life response rate (43 vs 18%); time to PSA progression (8.3 vs 3.0 months); radiographic progression-free survival (8.3 vs 2.9 months); and time to first skeletal event (16.7 vs 13.3 months).
Patients given the androgen receptor-signaling inhibitor had higher rates of all grades of fatigue, diarrhea, musculoskeletal pain, headache, and hot flashes than controls. Five (0.6%) patients given enzalutamide experienced seizures, although predisposing factors were noted in most of these men.
Commenting on the findings, Alan Ashworth, chief executive of The Institute of Cancer Research, one of two sites where the trial was conducted, said in a press statement: "What we're seeing now is an unprecedented period of success for prostate cancer research, with four new drugs shown to extend life in major clinical trials in just two years, and several others showing promise.
"It truly is a golden age for prostate cancer drug discovery and development."
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