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.
To determine whether age is associated with clinical outcomes in mHSPC.
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.
Randomization 1:1 to enzalutamide (160 mg/d) plus ADT or placebo plus ADT; stratification by disease volume and prior docetaxel use.
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).
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.
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.
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.
European urology oncology. 2023 Dec 09 [Epub ahead of print]
Francisco Gomez-Veiga, Russell Z Szmulewitz, Jeffrey Holzbeierlein, Arun A Azad, Taro Iguchi, Arnauld Villers, Antonio Alcaraz, Boris Alekseev, Neal D Shore, Brad Rosbrook, Fabian Zohren, Jie Ma, Gabriel P Haas, Arnulf Stenzl, Andrew J Armstrong
Complexo Hospitalario Universitario de A Coruña, Coruña, Spain. Electronic address: ., The University of Chicago, Chicago, IL, USA., The University of Kansas Medical Center, Kansas City, KS, USA., Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Kanazawa Medical University, Ishikawa, Japan., University Hospital Centre, Lille University, Lille, France., Hospital Clinic de Barcelona, Barcelona, Spain., Hertzen Moscow Cancer Research Institute, Moscow, Russia., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Pfizer Inc., San Diego, CA, USA., Astellas Pharma Inc., Northbrook, IL, USA., University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany., Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University, Durham, NC, USA.