TY - JOUR

T1 - Fatigue, health-related quality-of-life and metabolic changes in men treated with enzalutamide or abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer

T2 - A randomised clinical trial (HEAT)

AU - Ternov, Klara K.

AU - Sønksen, Jens

AU - Fode, Mikkel

AU - Lindberg, Henriette

AU - Kistorp, Caroline

AU - Bisbjerg, Rasmus

AU - Faber, Jens

AU - Klausen, Tobias W.

AU - Palapattu, Ganesh

AU - Østergren, Peter B.

N1 - Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022

Y1 - 2022

N2 - Introduction: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC). Herein, we compare fatigue, health-related quality-of-life (HRQoL) and metabolic changes in men with mCRPC treated with enzalutamide and AAP. Materials and methods: In this single-centre, open-labelled, phase IV trial, patients with metastatic prostate cancer progressing on androgen deprivation therapy were randomly assigned to enzalutamide (160 mg daily) or AAP (1000 mg abiraterone acetate and 10 mg prednisone daily) as first-line mCRPC treatment. The primary outcome was the difference in changed fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire). The secondary outcomes were differences in changed HRQoL (Functional Assessment of Cancer Therapy-Prostate questionnaire), body composition, weight, glucose homeostasis, lipid profile and blood pressure. All outcomes were assessed at baseline and at 12-week follow-up. Trial registration: clinicaltrialsregister.eu (2017-000099-27). Results: 170 patients were randomised (1:1) to enzalutamide or AAP. The primary outcome was positive with a clinically meaningful difference in fatigue, favouring AAP (3.4 points, 95% CI 1.2; 5.6, P = 0.003). The group difference in changed HRQoL did not reach clinical significance. The most important metabolic finding was a higher increase in glycated haemoglobin (HbA1c) for AAP than enzalutamide (3.4 mmol/mol, 95% CI 2.1; 4.8, P = 0.001). Eight patients developed type 2 diabetes (T2D) in the AAP group and none in the enzalutamide group. No treatment-related serious adverse event was observed. Conclusions: AAP resulted in less fatigue than enzalutamide in a randomised setting. This was at the expense of a higher HbA1c increase and incidence of T2D.

AB - Introduction: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC). Herein, we compare fatigue, health-related quality-of-life (HRQoL) and metabolic changes in men with mCRPC treated with enzalutamide and AAP. Materials and methods: In this single-centre, open-labelled, phase IV trial, patients with metastatic prostate cancer progressing on androgen deprivation therapy were randomly assigned to enzalutamide (160 mg daily) or AAP (1000 mg abiraterone acetate and 10 mg prednisone daily) as first-line mCRPC treatment. The primary outcome was the difference in changed fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire). The secondary outcomes were differences in changed HRQoL (Functional Assessment of Cancer Therapy-Prostate questionnaire), body composition, weight, glucose homeostasis, lipid profile and blood pressure. All outcomes were assessed at baseline and at 12-week follow-up. Trial registration: clinicaltrialsregister.eu (2017-000099-27). Results: 170 patients were randomised (1:1) to enzalutamide or AAP. The primary outcome was positive with a clinically meaningful difference in fatigue, favouring AAP (3.4 points, 95% CI 1.2; 5.6, P = 0.003). The group difference in changed HRQoL did not reach clinical significance. The most important metabolic finding was a higher increase in glycated haemoglobin (HbA1c) for AAP than enzalutamide (3.4 mmol/mol, 95% CI 2.1; 4.8, P = 0.001). Eight patients developed type 2 diabetes (T2D) in the AAP group and none in the enzalutamide group. No treatment-related serious adverse event was observed. Conclusions: AAP resulted in less fatigue than enzalutamide in a randomised setting. This was at the expense of a higher HbA1c increase and incidence of T2D.

KW - Abiraterone

KW - Castration-resistant

KW - Enzalutamide

KW - Fatigue

KW - Metabolic changes

KW - Prostate cancer

KW - Quality-of-life

U2 - 10.1016/j.ejca.2022.04.034

DO - 10.1016/j.ejca.2022.04.034

M3 - Journal article

C2 - 35709600

AN - SCOPUS:85132706005

VL - 171

SP - 75

EP - 84

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

SN - 0959-8049

ER -