A Phase 3 Trial Shows that Xtandi Reduces the Risk of Metastasis in Hormone-Resistant Prostate Cancer
According to results just recently presented at the February 2018 Genitourinary Cancers Symposium in San Francisco, treatment with Xtandi® (enzalutamide) reduced the risk of metastasis or death in hormone-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 clinical trial evaluated whether adding Xtandi® to the standard androgen (hormone) deprivation therapy (ADT) was better than ADT alone in patients whose cancer had progressed based on rising PSA levels. The 1,401 men in the study had increasing PSA levels, but no symptoms nor prior evidence of metastases. The Xtandi® – ADT combination extended the time a patient remained alive and metastasis-free by nearly two years, compared to ADT alone. Patients with non-metastatic, hormone-resistant cancer are those whose prostate cancer worsens despite reduction of the amount of testosterone to very low levels with anti-androgen therapies. In such 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 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). 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.
Side effects 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 combination treatment also reported three seizures (none in those taking ADT alone). Treatment discontinuation primarily due to adverse events was low with both treatments.