The supplemental New Drug Application for enzalutamide, an androgen receptor inhibitor, has been accepted for filing and granted Priority Review designation by the FDA. If approved, it would expand the indication of enzalutamide to include men with non-metastatic castration-resistant prostate cancer (CRPC) based on data from the phase III PROSPER trial (NCT02003924). Enzalutamide is currently indicated for the treatment of patients with metastatic CRPC.
Prostate cancer is the second most common cancer in men worldwide. More than 164,000 men in the U.S. are estimated to be newly diagnosed with prostate cancer in 2018. 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 (PSA) level. Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.
The PROSPER trial evaluated enzalutamide plus androgen deprivation therapy (ADT) versus ADT alone in 1,401 patients with non-metastatic CRPC. The study met its primary endpoint, demonstrating that the use of enzalutamide plus ADT significantly reduced the risk of developing metastasis or death compared to ADT alone.
Adverse events in the PROSPER trial were higher in the enzalutamide plus ADT arm compared to ADT alone (87% vs. 77%), and they were generally consistent with those reported in prior enzalutamide clinical trials in patients with metastatic CRPC. Results from the PROSPER trial were presented at the 2018 Genitourinary Cancers Symposium in February.
"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 U.S.," said Maha Hussain, MD, Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, who presented 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."
The FDA approved enzalutamide in 2012 for the treatment of patients with metastatic CRPC who had previously received docetaxel. In 2014, the FDA approved enzalutamide to treat patients with metastatic CRPC.
The FDA grants Priority Review designation to applications for drugs that, if approved, may offer significant improvements in the safety and effectiveness of the treatment of serious conditions when compared to standard applications.