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

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)

Source: DOI: 10.1200/JCO.21.00941 Journal of Clinical Oncology Published online December 20, 2021. PMID: 34928708

Dr. Lucio Gordan's Thoughts

Interesting and common scenario in clinic. Self-reported symptoms do exist but delaying disease-progression may have salutary benefits in the long haul insofar as using dual androgen-deprivation therapy.

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).

METHODS

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).

RESULTS

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.

CONCLUSION

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 Affiliations

¹NHMRC 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

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