Author(s): Martin R. Stockler, MBBS, MSc1; Andrew J. Martin, MBBS, PhD1; Ian D. Davis, PhD2; Haryana M. Dhillon, BSc, MA, PhD3; Stephen D. Begbie, MBBS4; Kim N. Chi, MD5; Simon Chowdhury, MBBS, PhD6; Xanthi Coskinas, BHSc, MMedSc (Clin Epid)1; Mark Frydenberg, MBBS2; Wendy E. Hague, MBBS, MBA, PhD, GAICD1; Lisa G. Horvath, MBBS, PhD7; Anthony M. Joshua, BSc, MBBS, PhD8; Nicola J. Lawrence, MBChB, PhD9; Gavin M. Marx, BSc (Med), MBBS10; John McCaffrey, MBBCh, BAO11; Ray McDermott, MD, PhD12; Margaret McJannett, RN13; Scott A. North, MD14; Francis Parnis, MBBS15; Wendy R. Parulekar, MD16; David W. Pook, MBBS, MD17; M. Neil Reaume, BSc, MD, MSc18; Shahneen Sandhu, MBBS19; Alvin Tan, MBChB20; Thean Hsiang Tan, MBBS21; Alastair Thomson, BM22; Francisco Vera-Badillo, MD, MSc23; Scott G. Williams, MBBS, MD19; Diana G. Winter, BSc1; Sonia Yip, BSc, PhD1; Alison Y. Zhang, MBBS, MMed1; Robert R. Zielinski, MBBS24; and Christopher J. Sweeney, MBBS25 for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL).
HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression. Scores from week 4 to 156 were analyzed with repeated measures modeling to calculate group means and differences. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life (OHQL). HRQL scores range from 0 (lowest possible) to 100 (highest possible).
HRQL was assessed in 1,042 of 1,125 participants (93%). Differences in means favored control over enzalutamide for fatigue (5.2, 95% CI, 3.6 to 6.9; P < .001), cognitive function (4.0, 95% CI, 2.5 to 5.5; P < .001), and physical function (2.6, 95% CI, 1.3 to 3.9; P < .001), but not OHQL (1.2, 95% CI, −0.2 to 2.7; P = .1). Deterioration-free survival rates at 3 years, and log-rank P values comparing the whole distributions, favored enzalutamide over control for OHQL (31% v17%; P < .0001), cognitive function (31% v 20%; P = .001), and physical function (31% v 22%; P < .001), but not fatigue (24% v 18%; P = .16). The effects of enzalutamide on HRQL were independent of baseline characteristics.
Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not OHQL. Enzalutamide was associated with improved deterioration-free survival for OHQL, physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of HRQL.
Author Affiliations1NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
2Monash University, Melbourne, Victoria, Australia
3CEMPED: The University of Sydney Centre for Medical Psychology and Evidence-Based Decision-Making, Sydney, NSW, Australia
4Port Macquarie Base Hospital, Port Macquarie, New South Wales, Australia
5BC Cancer Agency Vancouver Centre, Vancouver, BC, Canada
6Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
7Chris O’Brien Lifehouse, Sydney, New South Wales, Australia
8Kinghorn Cancer Centre, St Vincent’s Hospital, Sydney, New South Wales, Australia
9Auckland District Health Board, Auckland, New Zealand
10Sydney Adventist Hospital, Sydney, NSW, Australia
11Cancer Trials Ireland, Dublin, Ireland
12St Vincent’s University Hospital, Dublin, Ireland
13ANZUP Cancer Trials Groups, Sydney, NSW, Australia
14Cross Cancer Institute, Edmonton, Alberta, Canada
15Adelaide Cancer Centre, Adelaide, South Australia, Australia
16Canadian Cancer Trials Group, Kingston, Ontario, Canada
17Monash Health, Melbourne, Victoria, Australia
18University of Ottawa, Ottawa, Ontario, Canada
19Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
20Waikato District Health Board, Hamilton, New Zealand
21Royal Adelaide Hospital, Adelaide, South Australia, Australia
22Royal Cornwall Hospital, Cornwall, United Kingdom
23Kingston Health Sciences Centre, Kingston, Ontario, Canada
24Orange Health Service, Orange, New South Wales, Australia
25Dana-Farber Cancer Institute, Boston, MA