Date: 2016-01-26
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the Journal of Clinical Oncology (JCO)
Company: Medivation (USA - CA) Astellas (Japan)
Product: Xtandi® (enzalutamide) and bicalutamide
Action
mechanism: Xtandi® (enzalutamide) is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. It has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to Xtandi®. Xtandi® decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.
Disease: prostate cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The Phase 2 STRIVE trial enrolled 396 castration-resistant prostate cancer patients in the United States. The trial randomized 257 patients with metastatic prostate cancer and 139 patients with non-metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The primary endpoint of the trial was progression-free survival, 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 occurs first. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily versus bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with a LHRH analogue. (NCT01664923)
Latest
news: * On January 26, 2016, Medivation and Astellas Pharma announced that results from the STRIVE trial of enzalutamide compared to bicalutamide in men with castration-resistant prostate cancer (CRPC) were published in the Journal of Clinical Oncology. The article is titled, "Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial". The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared with bicalutamide (Hazard Ratio = 0.24; 95% Confidence Interval, 0.18-0.32; p < 0.0001). Median PFS was 19.4 months in the enzalutamide group compared with 5.7 months in the bicalutamide group. The median time on treatment in the STRIVE trial was 14.7 months in the enzalutamide group versus 8.4 months in the bicalutamide group. Serious adverse events were reported in 29.4% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.1% of enzalutamide-treated patients versus 4.0% of bicalutamide-treated patients. One seizure was reported in the trial in the enzalutamide-treated group and none in the bicalutamide-treated 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. The STRIVE study is the second of two head-to-head studies of enzalutamide versus bicalutamide, the first of which was TERRAIN, which was published in the January 13, 2016 online issue of Lancet Oncology. * On May 17, 2015, Medivation and Astellas Pharma announced data from the Phase 2 STRIVE trial comparing enzalutamide and bicalutamide in non-metastatic (M0) and metastatic (M1) prostate cancer patients whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The data were presented during an oral plenary session at the 2015 American Urology Association (AUA) annual meeting in New Orleans, Louisiana. Title: A multicenter phase 2 study of enzalutamide versus bicalutamide in men with nonmetastatic or metastatic castration-resistant prostate cancer: STRIVE trial. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared with bicalutamide (Hazard Ratio = 0.24; 95% Confidence Interval (CI), 0.18-0.32; p < 0.0001). The median PFS was 5.7 months in the bicalutamide arm and 19.4 months in the enzalutamide arm; * On April 2, 2015, Medivation and Astellas Pharma announced topline results from the Phase 2 STRIVE trial comparing enzalutamide with bicalutamide in a study population of men with non-metastatic or metastatic castration-resistant prostate cancer. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared with bicalutamide (Hazard Ratio = 0.24; 95% Confidence Interval, 0.18-0.32; p < 0.0001). Median PFS was 19.4 months in the enzalutamide group compared with 5.7 months in the bicalutamide group. The median time on treatment in the STRIVE trial was 14.7 months in the enzalutamide group versus 8.4 months in the bicalutamide group. Serious adverse events were reported in 29.4% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.1% of enzalutamide-treated patients versus 4.0% of bicalutamide-treated patients. One seizure was reported in the trial in the enzalutamide-treated group and none in the bicalutamide-treated 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. The STRIVE study is the second of two head-to-head studies of enzalutamide versus bicalutamide, the first of which was TERRAIN. Additional results from the STRIVE trial, including the secondary endpoints and safety data, will be submitted for presentation at upcoming medical conferences.
Treatment with enzalutamide also demonstrated significant improvement in the secondary endpoints of radiographic PFS, time to PSA progression, and PSA response rates compared to bicalutamide;
For the subset of patients with M0 disease, the median PFS was 8.6 months in the bicalutamide arm and, at the time of analysis, had not yet been reached for patients in the enzalutamide arm with a Hazard Ratio (HR) of 0.24 (95% CI, 0.14-0.42; p < 0.0001). For patients with M1 disease, the median PFS was 5.5 months in the bicalutamide arm and 16.5 months in the enzalutamide arm with a HR of 0.24 (95% CI, 0.17-0.34; p < 0.0001).
The safety profile of enzalutamide-treated patients in STRIVE was consistent with the known safety profile of enzalutamide:
The median duration of treatment was 14.7 months with enzalutamide and 8.4 months with bicalutamide.
Serious adverse events (AEs) were reported in 29.4% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients. Grade 3 or higher cardiac AEs were reported in 5.1% of enzalutamide-treated patients versus 4.0% of bicalutamide-treated patients. One seizure was reported in the enzalutamide group and none in the bicalutamide 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.
