Sunday June 30, 2019 from 11:50 to 12:50
Phase 3 study of androgen-deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial
Cristiano Ferrario1, Andrew J. Armstrong2, Russell Szmulewitz3, Daniel Petrylak4, Arnauld Villers5, Arun Azad6, Antonio Alcaraz7, Boris Alekseev8, Taro Iguchi9, Neal D. Shore10, Brad Rosbrook11, Jennifer Sugg12, Benoit Baron13, Lucy Chen12, Arnulf Stenzl14.
1Jewish General Hospital and McGill University, Montréal, QC, Canada; 2Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, United States; 3The University of Chicago, Chicago, IL, United States; 4Yale Cancer Center, New Haven, CT, United States; 5University Hospital Centre, Lille University, Lille, France; 6Monash Health, Melbourne, Australia; 7Hospital Clinic de Barcelona, Barcelona, Spain; 8Hertzen Moscow Cancer Research Institute, Moscow, Russian Federation; 9Osaka City University Graduate School of Medicine, Osaka, Japan; 10Carolina Urologic Research Center, Myrtle Beach, SC, United States; 11Pfizer Inc., San Diego, CA, United States; 12Astellas Pharma Inc., Northbrook, IL, United States; 13Astellas Pharma Inc., Leiden, Netherlands; 14University Hospital, Eberhard Karls University, Tübingen, Germany
Introduction: Enzalutamide (ENZA), a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and non-metastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with androgen-deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) is unknown.
Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients with 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.
Results: A total of 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 followup was 14.4 months. ENZA + ADT significantly improved rPFS (Table 1); 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 1); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA patients vs. 24.7% of PBO patients with no unexpected AEs.
Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. 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.
This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Medical writing and editing assistance provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors..