Enzalutamide Superior to Bicalutamide in M0/M1 CRPC

Celestia S. Higano, MD

Enzalutamide (Xtandi) significantly improved progression-free survival (PFS) and PSA progression compared with bicalutamide in men with metastatic and non-metastatic castration-resistant prostate cancer (CRPC), according to findings from the STRIVE trial presented during the late-breaking abstract session at the 2015 American Urological Association (AUA) Annual Meeting.

In the phase II trial, the median PFS was 19.4 months with enzalutamide and 5.7 months with bicalutamide (hazard ratio [HR] = 0.24; 95% CI, 0.18-0.32;P<.0001). The median time to PSA progression in patients with M0 disease treated with enzalutamide was not reached compared with 11.1 months in the bicalutamide arm (HR = 0.18). In the M1 arm, PSA progression was seen at 24.9 months with enzalutamide versus 5.7 months with bicalutamide (HR = 0.19).

"Results from the STRIVE trial are of key interest to the medical community as they mark the second head-to-head trial of enzalutamide versus bicalutamide," co-principal investigator Celestia S. Higano, MD, professor, medicine and urology, University of Washington, said in a statement.

In the trial, 396 men with CRPC were evenly randomized to enzalutamide (n = 198) or bicalutamide (n = 198). The median age of patients was 73 years and 35% were M0 (n = 139). Overall, 70 patients with M0 disease and 128 with M1 CRPC were treated with enzalutamide. The median baseline PSA level was 12 ng/mL. The median duration of treatment was 14.7 months with enzalutamide and 8.4 months with bicalutamide.

Specifically in those with M1 disease (n = 257), the median PFS was 16.5 months for those treated with enzalutamide and 5.5 months with bicalutamide (HR = 0.24; 95% CI, 0.17-0.34;P<.0001). In those with M0 CRPC, the median PFS was not yet reached with enzalutamide versus 8.6 months with bicalutamide (HR = 0.24; 95% CI, 0.14-0.42;P<.0001).

Overall, 29.4% of patients treated with enzalutamide experienced a serious adverse event compared with 28.3% with bicalutamide. Grade 3 or higher cardiac toxicity was seen in 5.1% versus 4.0% for enzalutamide and bicalutamide, respectively. There was one seizure in the enzalutamide-treated patients compared with none in the bicalutamide arm.

"The analyses from STRIVE are in line with previous data from the TERRAIN trial demonstrating that patients treated with enzalutamide have improved clinical outcomes versus the common practice of adding bicalutamide to a luteinizing hormone-releasing hormone therapy," Higano said.

In the phase II TERRAIN study, 375 men with M1 CRPC received either enzalutamide (n = 184) or bicalutamide (n = 191). The median PFS was 15.7 months with enzalutamide compared with 5.8 months with bicalutamide (HR = 0.44; 95% CI, 0.34-0.57;P<.0001).

Median time on treatment was 11.7 and 5.8 months in the enzalutamide and bicalutamide arms, respectively. The median time to PSA progression was 19.4 versus 5.8 months for enzalutamide and bicalutamide, respectively (HR = 0.28;P.<0001).

Medivation, the developer of enzalutamide, has opened the phase III PROSPER trial to validate the efficacy of the antiandrogen in men with M0 CRPC. The study was initiated in December 2013 with the goal of enrolling approximately 1560 patients. In the study, patients are randomized in a 2:1 ratio between enzalutamide at 160 mg/day and placebo. The primary endpoint of the study is metastasis-free survival (NCT02003924).

References:

1. Shore ND, Heidenreich A, Villers A, et al. TERRAIN Trial: Prostate-specific Antigen Kinetics and Quality of Life Results of Enzalutamide versus Bicalutamide in Metastatic Castration-resistant Prostate Cancer. Presented at: 2015 AUA Annual Meeting; 2015 15-19; New Orleans, LA. Abstract PII-LBA4.
2. Penson D, Armstrong AJ, Concepcion R, et al. A Multicenter Phase 2 Study of Enzalutamide (ENZA) versus Bicalutamide (BIC) in Men with Nonmetastatic (M0) or Metastatic (M1) Castration-Resistant Prostate Cancer (CRPC): the STRIVE Trial. Presented at: 2015 AUA Annual Meeting; 2015 15-19; New Orleans, LA. Abstract PII-LBA10.