| General information |
| Database: | DB00238 |
| Objective: | Enzalutamide (formerly called MDV3100) targets multiple steps in the androgenreceptorsignaling pathway, the major driver of prostatecancer growth. They aimed to evaluate whether enzalutamide prolongs survival in men with castrationresistant prostate cancer after chemotherapy. |
| Authors: | Scher HI, et al |
| Title: | Increased survival with enzalutamide in prostate cancer after chemotherapy. |
| Journal: | N Engl J Med |
| Year: | 2012 |
| PMID: | 22894553 |
| Trial Design |
| Clinical Trial Id: | NCT00974311 |
| Agent: | enzalutamide (formerly called MDV3100)
|
| Target: | androgenreceptor
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an international, phase III, randomized, doubleblind, placebocontrolled study |
| Key Patients Feature: | patients at 156 sites in 15 countries with prostate cancer who had previously been treated with one or two chemotherapy regimens, at least one of which contained docetaxel |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | placebo |
| Treatment Info: | They randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). |
| Primary End Point: | overall survival. |
| Secondary End Point: | NA |
| Patients Number: | 1199 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | the proportion of patients with a reduction in the prostatespecific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the softtissue response rate (29% vs. 4%, P<0.001), the qualityoflife response rate (43% vs. 18%, P<0.001) |
| Disease Control Rate: | NA |
| Median Time to Progression: | the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), the time to the first skeletalrelated event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). |
| Median PFS A vs. C: | radiographic progression free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001) |
| Median OS A vs. C: | 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) versus 13.6 months (95% CI, 11.3 to 15.8) (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). |
| Adverse Event(agent arm): | Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide. |
| Conclusions: | Enzalutamide significantly prolonged the survival of men with metastatic castrationresistant prostate cancer after chemotherapy |