(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, will host the Prostate, Testicular, and Penile Cancer – Posters Session. Dr. Andrew J. Armstrong will present Abstract 5093: Predictors of treatment duration in patients with mHSPC treated with ENZA: A post hoc analysis of ARCHES.
Prior analyses from the phase 3 ARCHES trial demonstrated significant improvements in radiographic progression-free survival and overall survival with enzalutamide plus ADT compared with placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1 This post hoc analysis explored factors associated with varying durations of enzalutamide treatment exposure and evaluated reasons for treatment discontinuation over long-term follow-up.
Patients receiving enzalutamide were categorized according to treatment duration into short treatment (STx, 0–2 years), medium treatment (MTx, 2–5 years), and long treatment duration (LTx, >5 years). Among 572 enzalutamide-treated patients, 204 (36%) were classified as STx, 140 (24%) as MTx, and 228 (40%) as LTx.
Patients in the STx cohort were generally older and more likely to present with high-volume disease and ECOG performance status 1 compared with patients in the MTx and LTx groups. However, importantly, adverse disease features remained common even among patients with prolonged treatment exposure, as 55.3% of patients in the LTx cohort had high-volume disease and 73.2% had synchronous metastatic disease.
Achievement of deep PSA responses differed substantially according to treatment duration. A PSA nadir <0.2 ng/mL post-baseline was observed in 44.4% of STx patients, compared with 78.9% in the MTx group and 91.4% among patients receiving long-term therapy. Similarly, ECOG PS 0 status was more common among patients with prolonged treatment duration.
Progressive disease represented the most common reason for treatment discontinuation across cohorts, occurring in 52.0% of STx patients, 45.0% of MTx patients, and only 8.3% of LTx patients. Adverse events and treatment withdrawal were the second most common reasons for discontinuation and were substantially more frequent in the STx cohort.
Drug-related treatment-emergent adverse events per 100 patient-years were highest among STx patients (156.0), compared with MTx (89.5) and LTx (47.1). Similarly, treatment-emergent adverse events leading to treatment discontinuation were more frequent in the STx group (12.4 per 100 patient-years) versus MTx (1.5) and LTx (0.1).
Rates of adverse events of special interest were also generally higher among patients with shorter treatment durations. Fatigue rates per 100 patient-years were 19.0 in STx patients compared with 10.7 and 4.8 in the MTx and LTx groups, respectively. Select cardiovascular events, falls, fractures, and convulsions were also numerically more frequent among STx patients.
Key Messages:
- Patients receiving prolonged enzalutamide treatment generally demonstrated more favorable baseline and disease characteristics compared with patients with shorter treatment exposure
- Nevertheless, many long-term responders still harbored adverse prognostic features, including high-volume and synchronous metastatic disease
- Progressive disease remained the most common reason for treatment discontinuation across all groups
- Adverse events and treatment withdrawal represented the second leading cause of treatment discontinuation and were substantially more common among patients with short treatment duration
- Rates of treatment-emergent adverse events and adverse events of special interest were generally highest in the short-treatment cohort
- Optimal management of adverse events, comorbidities, and dose modifications may help improve long-term treatment persistence with enzalutamide in patients with mHSPC
Presented by: Andrew Armstrong, MD, MSc, Medical Oncologist, Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Duke Cancer Institute, Center for Prostate and Urologic Cancers, Durham, NC
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
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