Martin R Stockler1, Andrew J Martin1, Ian D Davis2, Haryana M Dhillon3, Stephen D Begbie4, Kim N Chi5, Simon Chowdhury6, Xanthi Coskinas1, Mark Frydenberg2, Wendy E Hague1, Lisa G Horvath7, Anthony M Joshua8, Nicola J Lawrence9, Gavin M Marx10, John McCaffrey11, Ray McDermott12, Margaret McJannett13, Scott A North14, Francis Parnis15, Wendy R Parulekar16, David W Pook17, M Neil Reaume18, Shahneen Sandhu19, Alvin Tan20, Thean Hsiang Tan21, Alastair Thomson22, Francisco Vera-Badillo23, Scott G Williams19, Diana G Winter1, Sonia Yip1, Alison Y Zhang1, Robert R Zielinski24, Christopher J Sweeney25. 1. NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. 2. Monash University, Melbourne, Victoria, Australia. 3. CEMPED: The University of Sydney Centre for Medical Psychology and Evidence-Based Decision-Making, Sydney, NSW, Australia. 4. Port Macquarie Base Hospital, Port Macquarie, New South Wales, Australia. 5. BC Cancer Agency Vancouver Centre, Vancouver, BC, Canada. 6. Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 7. Chris O'Brien Lifehouse, Sydney, New South Wales, Australia. 8. Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, New South Wales, Australia. 9. Auckland District Health Board, Auckland, New Zealand. 10. Sydney Adventist Hospital, Sydney, NSW, Australia. 11. Cancer Trials Ireland, Dublin, Ireland. 12. St Vincent's University Hospital, Dublin, Ireland. 13. ANZUP Cancer Trials Groups, Sydney, NSW, Australia. 14. Cross Cancer Institute, Edmonton, Alberta, Canada. 15. Adelaide Cancer Centre, Adelaide, South Australia, Australia. 16. Canadian Cancer Trials Group, Kingston, Ontario, Canada. 17. Monash Health, Melbourne, Victoria, Australia. 18. University of Ottawa, Ottawa, Ontario, Canada. 19. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 20. Waikato District Health Board, Hamilton, New Zealand. 21. Royal Adelaide Hospital, Adelaide, South Australia, Australia. 22. Royal Cornwall Hospital, Cornwall, United Kingdom. 23. Kingston Health Sciences Centre, Kingston, Ontario, Canada. 24. Orange Health Service, Orange, New South Wales, Australia. 25. Dana-Farber Cancer Institute, Boston, MA.
Abstract
PURPOSE: 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% 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. 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.
PURPOSE: 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% 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. 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.
Authors: Rebecca Mercieca-Bebber; Daniel Sj Costa; Richard Norman; Monika Janda; David P Smith; Peter Grimison; Eva-Marie Gamper; Madeleine T King Journal: Med J Aust Date: 2019-06-02 Impact factor: 7.738
Authors: Ian D Davis; Andrew J Martin; Martin R Stockler; Stephen Begbie; Kim N Chi; Simon Chowdhury; Xanthi Coskinas; Mark Frydenberg; Wendy E Hague; Lisa G Horvath; Anthony M Joshua; Nicola J Lawrence; Gavin Marx; John McCaffrey; Ray McDermott; Margaret McJannett; Scott A North; Francis Parnis; Wendy Parulekar; David W Pook; M Neil Reaume; Shahneen K Sandhu; Alvin Tan; T Hsiang Tan; Alastair Thomson; Emily Tu; Francisco Vera-Badillo; Scott G Williams; Sonia Yip; Alison Y Zhang; Robert R Zielinski; Christopher J Sweeney Journal: N Engl J Med Date: 2019-06-02 Impact factor: 91.245
Authors: Andrew J Martin; Emma Gibbs; Katrin Sjoquist; Nick Pavlakis; John Simes; Tim Price; Jenny Shannon; Sanjeev Gill; Vikram Jain; Geoffrey Liu; George Kannourakis; Yeul Hong Kim; Jin Won Kim; David Goldstein Journal: Gastric Cancer Date: 2017-08-16 Impact factor: 7.370
Authors: Kim N Chi; Andrew Protheroe; Alfredo Rodríguez-Antolín; Gaetano Facchini; Henrik Suttman; Nobuaki Matsubara; Zhangqun Ye; Bhumsuk Keam; Ronaldo Damião; Tracy Li; Kelly McQuarrie; Bin Jia; Peter De Porre; Jason Martin; Mary B Todd; Karim Fizazi Journal: Lancet Oncol Date: 2018-01-08 Impact factor: 41.316
Authors: Howard I Scher; Karim Fizazi; Fred Saad; Mary-Ellen Taplin; Cora N Sternberg; Kurt Miller; Ronald de Wit; Peter Mulders; Kim N Chi; Neal D Shore; Andrew J Armstrong; Thomas W Flaig; Aude Fléchon; Paul Mainwaring; Mark Fleming; John D Hainsworth; Mohammad Hirmand; Bryan Selby; Lynn Seely; Johann S de Bono Journal: N Engl J Med Date: 2012-08-15 Impact factor: 91.245
Authors: N K Aaronson; S Ahmedzai; B Bergman; M Bullinger; A Cull; N J Duez; A Filiberti; H Flechtner; S B Fleishman; J C de Haes Journal: J Natl Cancer Inst Date: 1993-03-03 Impact factor: 13.506
Authors: George van Andel; Andrew Bottomley; Sophie D Fosså; Fabio Efficace; Corneel Coens; Stephane Guerif; Howard Kynaston; Paolo Gontero; George Thalmann; Atif Akdas; Sven D'Haese; Neil K Aaronson Journal: Eur J Cancer Date: 2008-09-05 Impact factor: 9.162
Authors: Arnulf Stenzl; Curtis Dunshee; Ugo De Giorgi; Boris Alekseev; Taro Iguchi; Russell Z Szmulewitz; Thomas W Flaig; Bertrand Tombal; Robert Morlock; Cristina Ivanescu; Krishnan Ramaswamy; Fred Saad; Andrew J Armstrong Journal: Eur Urol Date: 2020-04-23 Impact factor: 20.096
Authors: M F Janssen; A Simon Pickard; Dominik Golicki; Claire Gudex; Maciej Niewada; Luciana Scalone; Paul Swinburn; Jan Busschbach Journal: Qual Life Res Date: 2012-11-25 Impact factor: 4.147
Authors: Peter C Black; Nazanin Fallah-Rad; Andrew Loblaw; Elie Kassouf; Mira Keyes; Naveen S Basappa; Anand Swaminath Journal: Can Urol Assoc J Date: 2022-09 Impact factor: 2.052