Treatment with enzalutamide was associated with worsening of self-reported fatigue, physical function, and cognitive function, but not overall health and quality of life (OHQL), in patients with metastatic hormone-sensitive prostate cancer (HSPC) enrolled in the ENZAMET trial. These results were published in the Journal of Clinical Oncology.1
The phase 3 ENZAMET trial (ClinicalTrials.gov Identifier: NCT02446405) included 1125 patients with metastatic HSPC. They were randomly assigned 1:1 to receive enzalutamide (160 mg daily) or active control (physician’s choice of bicalutamide, flutamide, or nilutamide).
Patients in both arms received luteinizing hormone-releasing hormone analogue or underwent surgical castration. Baseline characteristics were similar between the arms.
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Previously published results showed longer overall survival and progression-free survival with enzalutamide.2 In the current analysis, researchers evaluated health-related quality of life (HRQL) in both treatment arms.1
HRQL was assessed at baseline, weeks 4 and 12, and then every 12 weeks until clinical progression using the European Organisation for Research and Treatment of Cancer core quality of life questionnaire. The questionnaire measures quality of life as related to functioning (physical, role, cognitive, emotional, and social), symptoms (fatigue, pain, and nausea and vomiting), and OHQL. HRQL was also assessed with the organization’s disease module for prostate cancer (QLM-PR25).
The proportion of patients who completed the HRQL questionnaire ranged from 93% at 4 weeks to 86% at 156 weeks. The median follow-up was 34 months.
There was a modest difference in OHQL score between the enzalutamide arm and the control arm (difference, 1.2; P =.10). The researchers observed a greater deterioration of the score at 12 weeks in the enzalutamide arm (difference, 1.9; P =.07), but values remained relatively stable after that.
The differences in overall means for the functional domains favored the control arm for physical functioning (2.6; P <.001), role functioning (3.6; P =.001), social functioning (3.3; P <.001), and cognitive functioning (4.0; P <.001), but not for emotional functioning (P =.8).
The differences in overall means for selected symptoms favored the control arm for fatigue (5.2; P <.001), appetite loss (2.5; P =.001), urinary symptoms (1.9; P =.003), and dyspnea (1.8; P =.05). The arms were similar for pain, nausea and vomiting, insomnia, constipation, diarrhea, hormonal symptoms, and sexual activity or sexual dysfunction (all P >.08).
At 3 years, the deterioration-free survival rates favored enzalutamide over control for OHQL (31% vs 17%; P <.001), cognitive functioning (31% vs 20%; P <.001), and physical functioning (31% vs 22%; P =.0013), but not fatigue (24% vs 18%; P =.16). The effects of enzalutamide on HRQL were seen regardless of patients’ baseline characteristics.
“The adverse effects of enzalutamide on HRQL were additive to those of early docetaxel,” the researchers noted. “These effects were most evident early in the treatment course. Enzalutamide was associated with net benefits in deterioration-free survival at 3 years despite these effects on HRQL.”
Disclosures: This research was partly supported by Astellas. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
References
- 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
- Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121-131. doi:10.1056/NEJMoa1903835
