Treatment with Xtandi (enzalutamide) reduced the risk of metastasis or death in castration-resistant prostate cancer (CRPC) patients whose cancer has not yet spread beyond the prostate, Pfizer and Japan-based Astellas Pharma recently announced.

The Phase 3 PROSPER trial evaluated whether adding Xtandi to the standard androgen deprivation therapy (ADT) was better than ADT alone in patients whose cancer had progressed based on rising PSA levels. The combination extended the time a patient remained alive and metastasis-free by nearly two years, compared to ADT alone.

The positive results of the trial led to the submission of marketing applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

The study, “PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC),” was presented last week at the 2018 Genitourinary Cancers Symposium in San Francisco.

Patients with non-metastatic CRPC are those whose prostate cancer worsens despite reduction of the amount of testosterone to very low levels with anti-androgen therapies.

“In patients with non-metastatic CRPC, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer,” Maha Hussain, MD, a researcher in the program, said in a press release. “There are currently no approved systemic therapies for patients with non-metastatic CRPC in the U.S.”

The multi-national, double-blind PROSPER study (NCT02003924) assessed the safety and effectiveness of a once-daily, oral, 160 mg dose of Xtandi, an androgen receptor inhibitor approved for treatment of advanced prostate cancer, in 1,401 men with CRPC on standard treatment with androgen deprivation therapy (ADT).

All patients had increasing PSA levels, but no symptoms nor prior evidence of metastases.

Adding Xtandi to standard ADT reduced the risk of developing metastases or death by 71% compared with ADT alone. Specifically, the combo treatment extended the time until a patient developed metastasis or died – the study’s primary endpoint – from 14.7 months to 36.6 months.

Xtandi plus ADT also led to a 93% decrease in the relative risk of PSA worsening, delayed median time to PSA progression by 33.3 months, and prolonged median time to first use of antineoplastic (anticancer) therapy by 21.9 months, compared to ADT alone. Subsequent follow-up will enable the analysis of changes in overall survival, another of the study’s secondary endpoints.

The adverse events with Xtandi were consistent with those reported in prior studies in patients with metastatic CRPC taking this medication.

Grade 3 (severe) or higher adverse events were observed in 31% of men taking Xtandi plus ADT, compared to 23% with ADT alone. The most frequent severe events were hypertension and fatigue.

In addition, major adverse cardiovascular events occurred in 5% of patients receiving Xtandi plus ADT – compared to 3% with ADT alone. The group taking the combo treatment also reported three seizures (none in those taking ADT alone).

Treatment discontinuation primarily due to adverse events was low with both treatments.