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.
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.
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.
The addition of ENZA maintained GHQL and improved deterioration-free survival because early impairments in specific aspects of HRQL were insufficient to outweigh the subsequent benefits of delayed clinical progression.
ACTRN12614000110684, NCT02446405; EUCTR2014-003190-42-IE.
ANZUP Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney.
Astellas Pharma.
M.R. Stockler: Research grant / Funding (institution): Astellas; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Bayer. A.J. Martin: Research grant / Funding (institution): Astellas. I.D. Davis: Research grant / Funding (institution): Astellas. K.N. Chi: Research grant / Funding (institution): Astellas. S. Chowdhury: Research grant / Funding (institution): Astellas. L.G. Horvath: Research grant / Funding (institution): Astellas. N.J. Lawrence: Research grant / Funding (institution): Astellas. G.M. Marx: Research grant / Funding (institution): Astellas. J. Mc Caffrey: Research grant / Funding (institution): Astellas. R. McDermott: Research grant / Funding (institution): Astellas. S.A. North: Research grant / Funding (institution): Astellas. F. Parnis: Research grant / Funding (institution): Astellas. D.W. Pook: Research grant / Funding (institution): Astellas. M.N. Reaume: Research grant / Funding (institution): Astellas. S.K. Sandhu: Research grant / Funding (institution): Astellas. T.H. Tan: Research grant / Funding (institution): Astellas. A. Thomson: Research grant / Funding (institution): Astellas. R. Zielinski: Research grant / Funding (institution): Astellas. C.J. Sweeney: Research grant / Funding (institution): Astellas. All other authors have declared no conflicts of interest.