Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged <75 and ≥75 Years: ARCHES Post Hoc Analysis
- Author(s)
- Gomez-Veiga, F; Szmulewitz, RZ; Holzbeierlein, J; Azad, AA; Iguchi, T; Villers, A; Alcaraz, A; Alekseev, B; Shore, ND; Rosbrook, B; Zohren, F; Ma, J; Haas, GP; Stenzl, A; Armstrong, AJ;
- Details
- Publication Year 2024-08,Volume 7,Issue #4,Page 860-869
- Journal Title
- European Urology Oncology
- Publication Type
- Research article
- Abstract
- BACKGROUND: In ARCHES, treatment intensification of androgen deprivation therapy (ADT) with enzalutamide versus placebo improved clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Understanding the benefits and tolerability of enzalutamide for men aged ≥75 yr may inform disease management. OBJECTIVE: To determine whether age is associated with clinical outcomes in mHSPC. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of the multinational, double-blind, randomized, placebo-controlled, phase 3 ARCHES trial in 1150 men with mHSPC (median follow-up [mo]: <75 yr, 44.6; ≥75 yr, 44.3) was performed. INTERVENTION: Randomization 1:1 to enzalutamide (160 mg/d) plus ADT or placebo plus ADT; stratification by disease volume and prior docetaxel use. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), radiographic progression-free survival (rPFS), safety, and other secondary endpoints were compared between age groups (<75 and ≥75 yr) and treatment arms (Cox proportional hazard models). RESULTS AND LIMITATIONS: Men aged <75 versus ≥75 yr had longer OS (enzalutamide plus ADT: hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.47-0.91; p = 0.02; placebo plus ADT: HR 0.81; 95% CI 0.60-1.09; p = 0.13) and rPFS (enzalutamide plus ADT: HR 0.78; 95% CI 0.58-1.04; p = 0.12; placebo plus ADT: HR 0.98; 95% CI 0.74-1.30; p = 0.007). Enzalutamide improved OS (<75 yr: HR 0.61; 95% CI 0.47-0.79; ≥75 yr: HR 0.76; 95% CI 0.54-1.09) and secondary efficacy endpoints without evidence of statistical heterogeneity, and was generally well tolerated in both age groups, with minimal quality-of-life impact. Older versus younger patients experienced more frequent dose interruptions (20.2% vs 10.9%) and treatment-emergent adverse events (95.2% vs 89.1%). Post hoc examination and small sample size preclude definitive conclusions. CONCLUSIONS: Enzalutamide plus ADT improved efficacy outcomes and was generally well tolerated despite shorter treatment exposure in older patients, indicating enzalutamide's utility in patients with mHSPC aged <75 and ≥75 yr. PATIENT SUMMARY: Enzalutamide is a drug approved to treat men with prostate cancer. In this report, we compared patients aged <75 and ≥75 yr treated with enzalutamide plus androgen deprivation therapy to determine whether age affected how long they lived without the cancer spreading to other parts of their body. We found that, although younger patients had more favorable survival outcomes, enzalutamide was associated with longer survival and reduced disease spread in both age groups.
- Publisher
- Elsevier
- Keywords
- Humans; Male; *Nitriles/therapeutic use; *Benzamides/therapeutic use; *Phenylthiohydantoin/therapeutic use; Aged; Double-Blind Method; Treatment Outcome; *Prostatic Neoplasms/drug therapy/pathology/mortality; Middle Aged; Aged, 80 and over; Age Factors; Neoplasm Metastasis; Androgen Antagonists/therapeutic use; Age; Enzalutamide; Metastatic hormone-sensitive prostate cancer; Overall survival; Progression-free survival; Treatment efficacy
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.euo.2023.11.012
- Open Access at Publisher's Site
https://doi.org/10.1016/j.euo.2023.11.012- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-01 05:00:16
Last Modified: 2024-08-01 05:00:43