151. Androgen deprivation therapy with enzalutamide or placebo in metastatic hormone-sensitive prostate cancer: ARCHES.
- Author
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Von Buren M., Alekseev B., Iguchi T., Shore N.D., Rosbrook B., Sugg J., Baron B., Chen L., Stenzl A., Azad A., Villers A., Petrylak D., Szmulewitz R., Armstrong A.J., Alcaraz A., Von Buren M., Alekseev B., Iguchi T., Shore N.D., Rosbrook B., Sugg J., Baron B., Chen L., Stenzl A., Azad A., Villers A., Petrylak D., Szmulewitz R., Armstrong A.J., and Alcaraz A.
- Abstract
Background: Enzalutamide (ENZA), a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Method(s): ARCHES is a multinational, double-blind, Phase 3 study (NCT02677896). Patients with metastatic hormone-sensitive prostate cancer (mHSPC) were randomized 1:1 to ENZA (160 mg/day) + ADT or placebo (PBO) + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS), assessed centrally, or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses, and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Result(s): 1150 men were randomized to ENZA (n = 574) or PBO (n = 576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease; 18% had prior docetaxel. Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region, and prior docetaxel (hazard ratios [HRs] 0.24-0.53). Secondary endpoints improved with ENZA + ADT (Table); overall survival data are immature. Grade 3-4 adverse events (AEs) were reported in 23.6% of ENZA patients versus 24.7% of PBO patients, with no unexpected AEs.(Table presented) Conclusion(s): ENZA + ADT significantly improved rPFS and other efficacy endpoints versus PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Funding(s): Astellas Pharma Inc. and Medivation LLC, a Pfizer Company. Medical writing: Complete HealthVizion.
- Published
- 2019