Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Arnulf Stenzl*, Tübingen, Germany, Russell Z. Szmulewitz, Chicago, IL, Daniel Petrylak, New Haven, CT, Jeffrey Holzbeierlein, Kansas City, KS, Arnauld Villers, Lille, France, Arun Azad, Melbourne, Victoria, Australia, Antonio Alcaraz, Barcelona, Spain, Boris Alekseev, Moscow, Russian Federation, Taro Iguchi, Osaka, Japan, Neal D. Shore, Myrtle Beach, SC, Brad Rosbrook, San Diego, CA, Benoit Baron, Leiden, Netherlands, Futoshi Kunieda, Robert Morlock, Northbrook, IL, Krishnan Ramaswamy, New York, NY, Andrew J. Armstrong, Durham, NC
Introduction: Potent androgen receptor inhibitor enzalutamide (ENZA) provides benefit in men with castration-resistant prostate cancer (CRPC). ARCHES, a multinational, double-blind, placebo (PBO)-controlled, Phase 3 study (NCT02677896), examined the efficacy of ENZA with androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). As an important marker of prostate cancer, here we report prostate-specific antigen (PSA) results for ARCHES.
Methods: Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel. Up to 3 months of ADT (≤6 months if with docetaxel) with no radiographic disease progression or rising PSA levels prior to day 1 was allowed. The primary endpoint was radiographic progression-free survival (rPFS) [scans assessed centrally] or death within 24 weeks of treatment discontinuation. Pre-specified analyses included rPFS (overall and by baseline PSA levels), time to PSA progression, time to castration resistance, PSA undetectable rate, and PSA reduction from baseline. Treatment continued until disease progression or unacceptable toxicity.
Results:1150 pts were randomized (ENZA + ADT, n=574; PBO + ADT, n=576). Baseline characteristics were balanced between groups; 91% had prior ADT. Overall median baseline PSA level was 5.21 ng/mL; median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS overall, regardless of baseline PSA level (Table). ENZA + ADT significantly improved time to PSA progression and time to castration resistance. The proportions of pts with undetectable PSA or PSA reduction ≥50% or ≥90% from baseline during the study were higher with ENZA + ADT. Adverse events were reported in 85.1% of ENZA + ADT pts vs 85.9% of PBO + ADT pts, with no unexpected adverse events.
Conclusions: ENZA + ADT significantly improved rPFS vs PBO + ADT in pts with mHSPC, regardless of baseline PSA level, suggesting the limitation of baseline PSA as a predictive factor in this population in which most pts received prior ADT. However, ENZA + ADT significantly improved PSA-related efficacy endpoints. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials.
Source of Funding: This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Medical writing and editorial assistance were provided by Caitlin Watson and Lauren Smith from Complete HealthVizion, funded by the study sponsors.