The results from the phase 3 PROSPER trial in patients with non-metastatic ( M0 ) castration-resistant prostate cancer ( CRPC ) were announced .
The results show that the use of Enzalutamide ( Xtandi ), an androgen receptor inhibitor, plus androgen deprivation therapy ( ADT ) has significantly reduced the risk of developing metastases or death by 71% compared to ADT alone.
The median for the primary endpoint, metastasis-free survival ( MFS ), was 36.6 months for men who received Enzalutamide compared to 14.7 months with ADT alone ( n=1401; hazard ratio, HR=0.29 [ 95% CI: 0.24-0.35 ]; p less than 0.0001 ).
In the PROSPER trial, treatment with Enzalutamide plus ADT delayed the development of metastases compared to standard of care ADT alone and, if approved, may provide men with non-metastatic CRPC an important new treatment option.
PROSPER also investigated time to prostate-specific antigen ( PSA ) progression, time to first use of new antineoplastic therapy and overall survival ( OS ) as key secondary endpoints.
The analysis demonstrated that patients who received Enzalutamide plus ADT had a 93% reduction in relative risk of PSA progression compared to patients who received ADT alone ( HR=0.07 [ 95% CI: 0.05-0.08]; P less than 0.0001 ).
Enzalutamide plus ADT delayed the median time to PSA progression by 33.3 months ( 37.2 months [ 95% CI: 33.1-NR ] versus 3.9 months with ADT alone [ 95% CI: 3.8-4.0 ] ).
Enzalutamide plus ADT prolonged the median time to first use of new antineoplastic therapy by 21.9 months versus ADT alone ( 39.6 months [ 95% CI: 37.7-NR ] vs. 17.7 months [ 95% CI: 16.2-19.7 ] ), a 79% relative risk reduction ( HR=0.21 [ 95% CI: 0.17-0.26 ]; p less than 0.0001 ).
At the time of the first interim analysis, median overall survival had not yet been reached in either treatment arm.
However, these interim results demonstrated a trend in favor of Enzalutamide that was not statistically significant ( HR=0.80 [ 95% CI: 0.58-1.09 ]; p=0.1519 ).
Adverse events in the PROSPER trial were generally consistent with those reported in prior Enzalutamide clinical trials in patients with metastatic CRPC.
Grade 3 or higher adverse events were reported in 31% of men treated with Enzalutamide plus ADT and in 23% of men treated with ADT alone.
The most common ( greater than or equal to 2% ) grade 3 or higher adverse events that were reported more often in Enzalutamide plus ADT-treated patients included hypertension ( 5% vs. 2% ) and fatigue ( 3% vs. 1% ).
Major adverse cardiovascular events were reported in 5% of patients who received Enzalutamide plus ADT and 3% with ADT alone.
Three seizures ( less than 1% ) were reported with Enzalutamide plus ADT patients and none were reported for those who received ADT alone.
The percentage of patients in whom adverse events were the primary reason leading to treatment discontinuation was low in both study arms ( 9% with Enzalutamide plus ADT versus 6% with ADT alone ).
PROSPER, a phase 3 randomized, double-blind, placebo-controlled, multi-national trial enrolled approximately 1,400 patients with non-metastatic castration-resistant prostate cancer at sites in the United States, Canada, Europe, South America and the Asia-Pacific region.
PROSPER enrolled patients with prostate cancer that had progressed, based on a rising prostate-specific antigen level despite androgen deprivation therapy, but who had no symptoms and no prior or present evidence of metastatic disease.
The trial evaluated Enzalutamide at a dose of 160 mg taken orally once daily plus ADT, versus placebo plus ADT.
The primary endpoint of the PROSPER trial, metastasis-free survival, is a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation. Secondary endpoints included time to PSA progression, time to first use of antineoplastic therapy and overall survival.
Prostate cancer is the second most common cancer in men worldwide. More than 164,000 men in the United States are estimated to be newly diagnosed with prostate cancer in 2018.
In the European Union, the estimated number of new prostate cancer cases in 2015 was 365,000.
Castration-resistant prostate cancer refers to the subset of men whose prostate cancer progresses despite castration levels of testosterone.
Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body, and there is a rising prostate-specific antigen level.
Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic castration-resistant prostate cancer. ( Xagena )
Source: Astellas, 2018