David F. Penson, MD
Treatment with enzalutamide reduced the risk of progression by 76% compared with bicalutamide in men with castration-resistant prostate cancer (CRPC), according to topline results from the phase II STRIVE study.
The STRIVE study enrolled 396 patients with non-metastatic (n = 139) and metastatic CRPC (n = 257) following progression on an LHRH analog or orchiectomy. Patients treated with enzalutamide had a median progression-free survival (PFS) of 19.4 months compared with 5.7 months in the bicalutamide arm (HR = 0.24; 95% CI, 0.18-0.32; P
< .0001). The median time on treatment was 14.7 months in the enzalutamide 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, MD, MPH, 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% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients experienced serious adverse events. Specifically, 5.1% of patients treated with enzalutamide experienced grade 3 or higher cardiac events, in contrast with 4.0% of bicalutamide-treated patents. One patient in the enzalutamide arm experienced a seizure, but no patients reported seizures in the comparator group.
The most common side effects noted more frequently in the enzalutamide-treated versus bicalutamide-treated patients included fatigue, back pain, hot flush, fall, hypertension, dizziness, and decreased appetite, consistent with the known safety profile of enzalutamide.
STRIVE is the second head-to-head phase II study to show an advantage for enzalutamide over bicalutamide. The first, labeled TERRAIN, compared enzalutamide and bicalutamide as a treatment for men with early mCRPC. In this 375-patient phase II trial, enzalutamide 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 enzalutamide was 15.7 versus 5.8 months with bicalutamide (HR = 0.44; 95% CI, 0.34-0.57). The median time to PSA progression was 19.4 months with enzalutamide compared with 5.8 months with bicalutamide (HR = 0.28). Additionally, 82% of enzalutamide-treated patients achieved ≥50% reduction in PSA from baseline by week 13 versus 21% of bicalutamide-treated patients. The median time on enzalutamide was 11.7 months compared with 5.8 months with bicalutamide.
Following the announcement of results from the TERRAIN trial, OncLive
interviewed Neal Shore, MD, co-principal investigator of the study and medical director, Carolina Urologic Research Center, on the necessity of a trial comparing enzalutamide and bicalutamide.
Shore explained the study was established to satisfy healthcare professionals and payers, who desired head-to-head data comparing the two drugs.
“The results from TERRAIN may help inform how clinicians treat metastatic castration-resistant prostate cancer patients after they fail LHRH therapy or surgical castration,” Shore said.
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 enzalutamide. Additional results from the STRIVE trial, including the secondary endpoints and safety data, will be submitted for presentation at upcoming medical conferences.