STRIVE Data Further Demonstrate PFS Benefit With Xtandi Over Bicalutamide

Treatment with Xtandi (enzalutamide) reduced the risk of progression by 76 percent compared with bicalutamide in men with castration-resistant prostate cancer (CRPC), according to topline results from the phase 2 STRIVE study.

The STRIVE study enrolled 396 patients with non-metastatic (n = 139) and metastatic CRPC following progression on an LHRH analog or orchiectomy. Patients treated with Xtandi had a median progression-free survival (PFS) of 19.4 months compared with 5.7 months in the bicalutamide arm. The median time on treatment was 14.7 months in the Xtandi arm compared with 8.4 months with bicalutamide.

“These results demonstrate the potential for enzalutamide to provide a longer duration of disease control compared with bicalutamide in the studied patient population,” co-principal investigator, David Penson, director of the Center for Surgical Quality and Outcomes Research and chair of the Department of Urologic Surgery of Vanderbilt University Medical Center, said in a statement.

In the STRIVE trial, patients were randomized to receive either 160 mg once daily enzalutamide or bicalutamide at 50 mg once daily. PFS was defined as time from randomization to radiographic (bone or soft tissue) progression, PSA progression (defined by Prostate Cancer Working Group 2 criteria), or death due to any cause, whichever occurred first.

In the safety analysis, 29.4 percent of Xtandi-treated patients and 28.3 percent of bicalutamide-treated patients experienced serious adverse events. Specifically, 5.1 percent of patients treated with Xtandi experienced grade 3 or higher cardiac events, in contrast with 4 percent of bicalutamide-treated patents. One patient in the Xtandi arm experienced a seizure, but no patients reported seizures in the comparator group.

The most common side effects noted more frequently in the Xtandi-treated versus bicalutamide-treated patients included fatigue, back pain, hot flush, fall, hypertension, dizziness and decreased appetite, consistent with the known safety profile of Xtandi.

STRIVE is the second head-to-head phase 2 study to show an advantage for Xtandi over bicalutamide. The first, labeled TERRAIN, compared Xtandi and bicalutamide as a treatment for men with early mCRPC. In this 375-patient phase 2 trial, Xtandi improved PFS by nearly 10 months compared with bicalutamide in patients with metastatic CRPC, according to results presented at the European Association of Urology in Madrid, Spain.

In TERRAIN, the median PFS with Xtandi was 15.7 versus 5.8 months with bicalutamide. The median time to PSA progression was 19.4 months with Xtandi compared with 5.8 months with bicalutamide. Additionally, 82 percent of Xtandi-treated patients achieved at least 50 percent reduction in PSA from baseline by week 13 versus 21 percent of bicalutamide-treated patients. The median time on Xtandi was 11.7 months compared with 5.8 months with bicalutamide.

Both STRIVE and TERRAIN enrolled patients with metastatic disease, but STRIVE was conducted in the United States, while TERRAIN was conducted in Canada and Europe. Findings from the STRIVE trial were announced by Medivation, Inc and Astellas Pharma Inc, the companies co-developing Xtandi. Additional results from the STRIVE trial, including the secondary endpoints and safety data, will be submitted for presentation at upcoming medical conferences.