ARCHES: Enzalutamide Plus ADT in Metastatic Hormone-Sensitive Prostate Cancer
As reported in the Journal of Clinical Oncology by Armstrong et al, findings from the phase III ARCHES trial have shown significant improvement in radiographic progression-free survival with enzalutamide plus androgen-deprivation therapy (ADT) vs placebo plus ADT in men with metastatic hormone-sensitive prostate cancer.
Study Details
In the double-blind trial, 1,150 patients from 202 sites were randomly assigned between March 2016 and January 2018 to receive enzalutamide 160 mg/day (n = 574) or placebo (n = 576) plus ADT. Randomization was stratified by disease volume and prior docetaxel therapy. In the enzalutamide/ADT and the placebo/ADT groups, 62% vs 65% had high disease volume and 2.4% vs 1.9% and 15.5% vs 15.8% had received one to five and six cycles of docetaxel, respectively. Treatment continued until radiographic progression, unacceptable toxicity, or initiation of an investigational agent or new prostate cancer therapy. The primary endpoint was radiographic progression-free survival on independent central review.
Findings
As of data cutoff in October 2018, median follow-up was 14.4 months. Radiographic progression-free survival was significantly improved in the enzalutamide/ADT vs placebo/ADT group, with median durations of not reached vs 19.0 months (hazard ratio [HR] = 0.39, P < .001). Similar benefits in radiographic progression-free survival were found among patients with high disease volume (HR = 0.43, 95% confidence interval [CI] = 0.33–0.57), low disease volume (HR = 0.25, 95% CI = 0.14–0.46), prior docetaxel (HR = 0.52, 95% CI = 0.30–0.89), and no prior docetaxel (HR = 0.37, 95% CI = 0.28–0.49).
Enzalutamide/ADT was also associated with reduced risks of prostate-specific antigen (PSA) progression (HR = 0.19, P < .001), initiation of new antineoplastic therapy (HR = 0.28, P < .001), first symptomatic skeletal event (HR = 0.52, P = .0026), and castration resistance (HR = 0.28, P < .001). More patients in the enzalutamide/ADT group achieved undetectable PSA level (68% vs 18%, P < .001) and objective response (83% vs 64%, P < .001). Overall survival data were immature at time of analysis.
Adverse Events
Grade ≥ 3 adverse events occurred in 24.3% of the enzalutamide/ADT group vs 25.6% of the placebo/ADT group, with the most common in the enzalutamide/ADT group being hypertension (3.3%). Serious adverse events occurred in 18.2% of the enzalutamide/ADT group vs 19.5% f the placebo/ADT group, and adverse events led to discontinuation of therapy in 7.2% vs 5.2%. Quality of life, assessed as mean Functional Assessment of Cancer Therapy–Prostate total score, was high at baseline and remained high over time in both groups.
The investigators concluded, “Enzalutamide [plus] ADT significantly reduced the risk of metastatic progression or death over time vs placebo plus ADT in men with [metastatic hormone-sensitive prostate cancer], including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.”
Andrew J. Armstrong, MD, ScM, of Duke University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Astellas Pharma and Pfizer. For full disclosures of the study authors, visit jco.ascopubs.org.
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®.
