Xtandi Reduces Risk of Metastasis or Death by 71% in Prostate Cancer Trial

Marketing applications for expansion of indication have been filed

Positive results have been announced from the phase 3 PROSPER trial in patients with nonmetastatic castration-resistant prostate cancer (CRPC). The results show that the use of enzalutamide (Xtandi, Astellas Pharma/Pfizer) plus androgen deprivation therapy (ADT) 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. Enzalutamide is currently approved only for patients with metastatic CRPC. Marketing applications for the new indication based on the results of the PROSPER study have been submitted to the FDA and the European Medicines Agency.

“In patients with nonmetastatic 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 nonmetastatic CRPC in the U.S.,” said Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, who will present the data this year. “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 nonmetastatic 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 with patients who received ADT alone. Enzalutamide plus ADT delayed the median time to PSA progression by 33.3 months versus 3.9 months with ADT alone.

Enzalutamide plus ADT prolonged the median time to first use of new antineoplastic therapy by 21.9 months versus ADT alone, a 79% relative risk reduction. 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 enzalutamide that was not statistically significant.

 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 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 were reported in 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).

 Source: Pfizer; February 5, 2018.