FDA to Review Application for Enzalutamide (Xtandi) in Metastatic Prostate Cancer

Approval decision expected in October

The FDA has accepted for review a supplemental new drug application for enzalutamide (Xtandi, Astellas Pharma/Medivation, Inc.) in men with metastatic castration-resistant prostate cancer (mCRPC), which includes findings from the phase 2 TERRAIN and STRIVE studies, to update the relevant clinical sections in the current labeling. Enzalutamide is approved by the FDA for the treatment of patients with mCRPC. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is October 22, 2016.

The TERRAIN trial enrolled 375 patients with metastatic prostate cancer whose disease had progressed despite luteinizing hormone-releasing hormone (LHRH) analogue therapy or after surgical castration. The trial’s primary endpoint was progression-free survival (PFS), defined as the time from randomization to centrally confirmed radiographic progression, a skeletal-related event, the initiation of new antineoplastic therapy, or death, whichever occurred first. The study was designed to evaluate oral enzalutamide administered at a dosage of 160 mg once daily, in comparison with bicalutamide administered at a dosage of 50 mg once daily (the approved dosage in combination with an LHRH analogue).

The STRIVE trial enrolled 396 patients with CRPC. A total of 257 patients had metastatic prostate cancer and 139 patients had nonmetastatic prostate cancer whose disease had progressed despite treatment with an LHRH analogue or after surgical castration. The study’s primary endpoint was PFS, defined as the time from randomization to radiographic (bone or soft- tissue) progression, prostate-specific antigen (PSA) progression (defined by Prostate Cancer Working Group 2 criteria), or death due to any cause, whichever occurred first. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily (n = 198) compared with bicalutamide at a dose of 50 mg taken once daily (n = 198), the approved dose in combination with an LHRH analogue.

Enzalutamide is approved by the FDA for the treatment of patients with mCRPC.

Enzalutamide is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within tumor cells. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and to inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this mechanism of action is unknown.

Source: Astellas Pharma; February 23, 2016.