Enzalutamide Improves Progression-Free Survival vs Bicalutamide in Nonmetastatic and Metastatic Castration-Resistant Prostate Cancer
Treatment with enzalutamide (Xtandi) tripled median progression-free survival vs bicalutamide in patients with nonmetastatic or metastatic castration-resistant prostate cancer, according to the phase II STRIVE trial reported in the Journal of Clinical Oncology by Penson et al.
Study Details
In the double-blind trial, 396 patients with nonmetastatic (n = 139) or metastatic disease (n = 257) from 62 U.S. sites were randomized between August 2012 and March 2014 to receive enzalutamide at 160 mg/d (n = 198) or bicalutamide at 50 mg/d (n = 198), with androgen-deprivation therapy continued in both groups. The primary endpoint was progression-free survival.
The enzalutamide and bicalutamide groups were generally balanced for age (median, 72 and 74 years; 39% and 49% ≥ 75 years), race/ethnicity (81% and 85% white), Eastern Cooperative Oncology Group performance status (0 for 75% and 73%, 1 for 25% and 27%), pain score (0–1 in 83% and 80%), Gleason score (8–10 in 51% and 49%), and disease localization (bone only in 31% and 33%, soft tissue only in 15% in both, both in 24% and 21%). Disease stage was M0 in 35% in both, including M0N0 in 31% and 30% and M1 in 65% in both.
Progression-Free Survival
Median time on treatment was 14.7 months in the enzalutamide group vs 8.4 months in the bicalutamide group. Median progression-free survival was 19.4 months (95% confidence interval [CI] = 16.5 months to not reached) in the enzalutamide group vs 5.7 months (95% CI = 5.6–8.1 months in the bicalutamide group (hazard ratio [HR] = 0.24, P < .001). Enzalutamide was associated with significant improvement in median time to prostate-specific antigen (PSA) progression (not reached vs 8.3 months [HR = 0.19, P < .001]), proportion of patients with a ≥ 50% PSA response (81% vs 31%, P < .001), and median radiographic progression-free survival (not reached vs 11.2 months [HR = 0.30, P < .001]).
In the 70 and 69 patients with nonmetastatic disease, median progression-free survival was not reached vs 8.6 months (HR = 0.24, P < .001), median time to PSA progression was not reached vs 11.1 months (HR = 0.18, P < .001), and median radiographic progression-free survival was not reached in either group (HR = 0.24, P < .001). In the 128 and 129 patients with metastatic disease, median progression-free survival was 16.5 vs 5.5 months (HR = 0.24, P < .001), median time to PSA progression was 24.9 vs 5.7 months (HR = 0.19, P < .001), and median radiographic progression-free survival was not reached vs 8.3 months (HR = 0.32, P < .001).
Adverse Events
Among adverse events of any grade, those reported more frequently with enzalutamide included fatigue (38% vs 28%), back pain (18% vs 16%), hot flashes (16% vs 10%), falls (14% vs 8%), hypertension (12% vs 5%), dizziness (12% vs 7%), and decreased appetite (12% vs 9%). Those reported more frequently with bicalutamide included constipation (17% vs 10%), diarrhea (14% vs 9%), anemia (11% vs 7%), and urinary tract infection (11% vs 5%). Adverse events of grade ≥ 3 occurred in 36% of patients in both the enzalutamide and bicalutamide groups, with the most common being fatigue (5% vs 3%), hypertension (5% vs 2%), and anemia (3% vs 5%).
Serious adverse events occurred in 29% vs 28%, and adverse events led to treatment discontinuation in 8% vs 6%. Adverse events led to death in 3% of patients in each group.
The investigators concluded: “Enzalutamide significantly reduced risk of prostate cancer progression or death compared with bicalutamide in patients with nonmetastatic or metastatic [castration-resistant prostate cancer].”
The study was funded by Medivation and Astellas Pharma Global Development.
David F. Penson, MD, MPH, of Vanderbilt University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
