Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by 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% v 17%; 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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021 Dec 20 [Epub ahead of print]

Martin R Stockler, Andrew J Martin, Ian D Davis, Haryana M Dhillon, Stephen D Begbie, Kim N Chi, Simon Chowdhury, Xanthi Coskinas, Mark Frydenberg, Wendy E Hague, Lisa G Horvath, Anthony M Joshua, Nicola J Lawrence, Gavin M Marx, John McCaffrey, Ray McDermott, Margaret McJannett, Scott A North, Francis Parnis, Wendy R Parulekar, David W Pook, M Neil Reaume, Shahneen Sandhu, Alvin Tan, Thean Hsiang Tan, Alastair Thomson, Francisco Vera-Badillo, Scott G Williams, Diana G Winter, Sonia Yip, Alison Y Zhang, Robert R Zielinski, Christopher J Sweeney, ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)

NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia., Monash University, Melbourne, Victoria, Australia., CEMPED: The University of Sydney Centre for Medical Psychology and Evidence-Based Decision-Making, Sydney, NSW, Australia., Port Macquarie Base Hospital, Port Macquarie, New South Wales, Australia., BC Cancer Agency Vancouver Centre, Vancouver, BC, Canada., Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Chris O'Brien Lifehouse, Sydney, New South Wales, Australia., Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, New South Wales, Australia., Auckland District Health Board, Auckland, New Zealand., Sydney Adventist Hospital, Sydney, NSW, Australia., Cancer Trials Ireland, Dublin, Ireland., St Vincent's University Hospital, Dublin, Ireland., ANZUP Cancer Trials Groups, Sydney, NSW, Australia., Cross Cancer Institute, Edmonton, Alberta, Canada., Adelaide Cancer Centre, Adelaide, South Australia, Australia., Canadian Cancer Trials Group, Kingston, Ontario, Canada., Monash Health, Melbourne, Victoria, Australia., University of Ottawa, Ottawa, Ontario, Canada., Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Waikato District Health Board, Hamilton, New Zealand., Royal Adelaide Hospital, Adelaide, South Australia, Australia., Royal Cornwall Hospital, Cornwall, United Kingdom., Kingston Health Sciences Centre, Kingston, Ontario, Canada., Orange Health Service, Orange, New South Wales, Australia., Dana-Farber Cancer Institute, Boston, MA.