Health-related quality of life (HRQL) in a randomized phase III trial of enzalutamide with standard first-line therapy for metastatic, hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led, international, co-operative group trial.

Background: We previously reported that treatment with enzalutamide (ENZA) rather than an older non-steroidal anti-androgen (NSAA: bicalutamide, nilutamide, or flutamide), resulted in longer overall survival when added to standard first-line treatment, with or without concurrent early docetaxel, in mHSPC (hazard ratio 0.67, 95% CI 0.52 to 0.86, p=0.002, NEJM 2019). Here we report effects on HRQL. Method(s): HRQL was measured with the EORTC QLQ-C30 and PR25 at weeks 0, 4, 12, and then 12-weekly until clinical progression. We used mixed models for repeated measures to calculate the least squares mean difference (LSMD), 95% CI, and p-value for comparisons of the randomly assigned groups for all assessments from week 4 to 156. For each analysis of deterioration-free survival, the endpoint was defined a-priori as the earliest of death, clinical progression, cessation of study treatment, or a 10-point worsening from baseline (minimum clinically important difference on scales scored from 0 to 100) in the pertinent HRQL sub-scale: physical functioning (PF), global health and quality of life (GHQL), cognitive functioning (CF), and fatigue; p-values were based on the log-rank test. Result(s): Completion of HRQL forms in 1016 men with a baseline assessment of HRQL (1125 randomised) ranged from 94% at week 12 to 78% at week 156. Random assignment to ENZA v NSAA was associated with modest impairments (LSMD, 95% CI) from week 4 to 156 in fatigue (5.0, 3.3 to 6.7, p<0.0001), CF (3.9, 2.4 to 5.4, p<0.0001), and PF (2.5, 1.2 to 3.8, p=0.0002), but not GHQL (1.1,-0.4 to 2.6, p=0.16). Deterioration-free survival rates at 3 years favoured ENZA over NSAA for GHQL (32% v 18%, p<0.0001), CF (33% v 21%, p=0.0003), and PF (31% v 22%, p=0.001), but not fatigue (26% v 18%, p=0.1). The effects of ENZA on HRQL were relatively stable over time and unaffected by treatment with concurrent early docetaxel. Conclusion(s): The addition of ENZA maintained GHQL and improved deteriorationfree survival b