As reported in the Journal of Clinical Oncology by Stockler et al, enzalutamide was associated with worsening in several quality-of-life domains—but not in overall health and quality of life—vs standard of care in the phase III ENZAMET trial evaluating the efficacy of the agent for patients with metastatic hormone-sensitive prostate cancer. Enzalutamide was, however, associated with better deterioration-free survival.

The ENZAMET trial showed that enzalutamide was associated with improved overall survival and progression-free survival vs standard of care.

Study Details

In the open-label trial, 1,125 patients were randomly assigned to receive either enzalutamide or physician’s choice of standard of care, with all patients receiving testosterone suppression. The current analysis included 1,042 patients (93% of population) with health-related quality of life data, including 520 in the enzalutamide group and 522 in the control group. Health-related quality of life was assessed with the EORTC core quality-of-life questionnaire and prostate-specific QLM-PR25 module at weeks 0, 4, 12, and then every 12 weeks until progression. Scores range from 0 to 100.

Deterioration-free survival was measured from random assignment until one of the following occurred earliest: death; clinical progression; discontinuation of study treatment; or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life.

Key Findings

Median follow-up was 34 months.

The effects of enzalutamide on health-related quality of life were independent of baseline characteristics.

Differences in mean changes from baseline in symptom domains showed poorer outcomes in the enzalutamide vs control group for fatigue (5.2, P < .001), appetite loss (2.5, P = .001), urinary symptoms (1.9, P = .003), and dyspnea (1.8,  P = .05), but not for pain, nausea and vomiting, insomnia, constipation, diarrhea, hormonal symptoms, or sexual activity or sexual dysfunction.

Differences in functional domains showed poorer outcomes in the enzalutamide group for cognitive function (4.0, P < .001), physical function (2.6, P < .001), role functioning (3.6, P < .001), and social functioning (3.3, P < .001), but not for emotional functioning.

No difference between groups was observed for overall health and quality of life (1.2, P = .1).

Deterioration-free survival rates at 3 years were better in the enzalutamide group for overall health and quality of life (31% vs 17%, P < .0001), cognitive function (31% vs 20%, P = .001), and physical function (31% vs 22%, P < .001), but not for fatigue (18% vs 24%, P = .16).

The investigators concluded: “Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not [overall health and quality of life]. Enzalutamide was associated with improved deterioration-free survival for [overall health and quality of life], physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of [health-related quality of life].

Martin R. Stockler, MBBS, MSc, of the NHMRC Clinical Trials Centre, University of Sydney, is the corresponding author for the Journal of Clinical Oncology article.  

Disclosure: The study was supported by Astellas. For full disclosures of the study articles, visit ascopubs.org.