Astellas Pharma and Pfizer have announced results from the phase 3 PROSPER trial in patients with non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC). The results show that the use of Xtandi (enzalutamide) plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastases or death by 71 per cent compared to ADT alone. The median for the primary endpoint, metastasis-free survival (MFS), was 36.6 months for men who received Xtandi compared to 14.7 months with ADT alone (n=1401; HR=0.29 [95% CI: 0.24-0.35]; p<0.0001). These data will be presented at the 2018 Genitourinary Cancers Symposium in San Francisco.

Marketing applications based on the results of the PROSPER study have been submitted to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA and EMA each have a filing review period during which they evaluate whether an application is complete and acceptable for filing. The data are also being submitted to additional regulatory authorities around the world.

“In patients with non-metastatic CRPC, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer. There are currently no approved systemic therapies for patients with non-metastatic CRPC in the US,” said Maha Hussain, M.D., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, who will present the data. “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 Xtandi plus ADT had a 93 per cent reduction in relative risk of PSA progression compared to patients who received ADT alone (HR=0.07 [95% CI: 0.05-0.08]; P<0.0001). Xtandi 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]).

Xtandi 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 per cent relative risk reduction (HR=0.21 [95% CI: 0.17-0.26]; p<0.0001). At the time of the first interim analysis, median OS had not yet been reached in either treatment arm. However, these interim results demonstrated a trend in favor of Xtandi 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 per cent of men treated with Xtandi plus ADT and in 23 per cent of men treated with ADT alone. The most common (=2%) Grade 3 or higher adverse events that were reported more often in Xtandi plus ADT-treated patients included hypertension (5% vs. 2%) and fatigue (3% vs. 1%). Major adverse cardiovascular events were reported in 5 per cent of patients who received Xtandi plus ADT and 3 per cent with ADT alone. Three seizures (<1%) were reported with Xtandi plus ADT patients and none were reported for those who received ADT alone. The per centage of patients in whom adverse events were the primary reason leading to treatment discontinuation was low in both study arms (9% with Xtandi plus ADT versus 6% with ADT alone).