Enzalutamide Associated with Worsened Cognitive/Physical Function but Not Overall HQL in mHSPC

Contemporary Concepts | Contemporary Concepts in Prostate Cancer | <b>Management of Survivorship & Quality of Life</b>

A health-related quality of life assessment found an association between worsened self-reported fatigue, cognitive function, and physical function, with enzalutamide treatment for patients with metastatic, hormone-sensitive prostate cancer but improved deterioration-free survival for overall health and quality of life.

An association was observed between enzalutamide (Xtandi) treatment and worsened self-reported fatigue, cognitive function, and physical function, although investigators noted an improvement in deterioration-free survival for overall health and quality of life (OHQL) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to results from the phase 3 ENZAMET trial (NCT02446405).1

The analyzed differences in means favored the control group over the enzalutamide group for fatigue (5.2; 95% CI, 3.6-6.9; P <.001), cognitive function (4.0; 95% CI, 2.5-5.5; P <.001), and physical function (2.6; 95% CI, 1.3-3.9; P <.001), but not OHQL (1.2; 95% CI, –0.2 to 2.7; P = .1).

“The addition of early enzalutamide to standard of care, including testosterone suppression with or without early docetaxel, improved overall survival during 3 years of follow-up with modest impairments in fatigue, physical function, and self-rated cognitive function, but not [ OHQL], in men with recently diagnosed, metastatic, hormone-sensitive prostate cancer,” the investigators wrote.

Previously reported data found enzalutamide improved overall survival when combined with standard of care for patients with mHSPC.2 Patients with prostate cancer with evident metastases on conventional imaging were randomized 1:1 receive daily enzalutamide at 160 mg or physician’s choice of bicalutamide, nilutamide, or flutamide.

Health-related quality of life (HRQOL) assessments occurred at baseline, 4 weeks, and 12 weeks, then every 12 weeks until clinical progression. The European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire included various items grouped into scales for functioning, symptoms, and OHQL.

HRQOL data were collected on December 31, 2019, with 93% of participants reporting HRQOL data. Baseline characteristics were similar among patients randomized to enzalutamide and control groups. The median follow up was 34 months.

Deterioration-free survival at 3 years favored the enzalutamide cohort vs the control cohort for OHQL (31% vs 17%; P <.0001), cognitive function (31% v 20%; P = .001), and physical function (31% v 22%; P <.001). Fatigue, however, was not (24% v 18%; P = .16) because disease progression delays outweighed the early deteriorations.

The study is limited because HRQOL was only assessed until progression and for a maximum of 3 years. HRQOL beyond progression is impacted by further treatments left to physicians.

“These impairments did not worsen over time, and better disease control improved deterioration-free survival rates at 3 years because the modest detrimental effects on aspects of HRQL were outweighed by subsequent delays in disease progression. Longer follow-up will reveal the effects of enzalutamide beyond 3 years,” the investigators concluded.


  1. Stockler MR, Martin AJ, Davis ID, et al. Health-related quality of life in metastatic, hormone-sensitive prostate cancer: ENZAMET (ANZUP 1304), an international, randomized phase III trial led by ANZUP. J Clin Oncol. Published online December 20, 2021. doi:10.1200/JCO.21.00941
  2. Davis ID, Martin AJ, Stockler MR, et al. ENZAMET trial investigators and the Australian and New Zealand urogenital and prostate cancer trials group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 2019;381:121-131.