Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged

Abstract

BackgroundIn 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. ObjectiveTo determine whether age is associated with clinical outcomes in mHSPC. Design, setting, and participantsA 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. InterventionRandomization 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 analysisOverall 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 limitationsMen 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. ConclusionsEnzalutamide 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 summaryEnzalutamide 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.