Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy☆,☆☆
Introduction
Along with prolongation of survival, improved health-related quality of life (HRQoL) is an important therapeutic objective for patients with metastatic castration-resistant prostate cancer (mCRPC) [1], [2], [3], due to concerns about the wide, varied spectrum of disease-related symptoms and the side-effects of therapy [4]. Assessment of HRQoL is increasingly incorporated into prospective studies of therapies for advanced prostate cancer [1], [3], [5], [6], [7], [8], [9] and patient-based questionnaires are considered more reliable and informative than interpretations assigned by study investigators [5]. Many novel therapies for mCRPC are available, namely abiraterone, cabazitaxel, enzalutamide and sipuleucel-T, but little is known about their impact on HRQoL.
Abiraterone acetate is a potent androgen biosynthesis inhibitor [10]. A recent randomised double-blind clinical trial of 1195 men with mCRPC progressing after docetaxel chemotherapy showed that abiraterone significantly prolonged overall survival compared with prednisone [11]. We present patient-reported data from the same trial, collected using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, in order to determine whether abiraterone improved HRQoL. Outcomes were reported using changes in the FACT-P and its subscales that have been established as clinically meaningful in this patient population.
Section snippets
Trial design
Study COU-AA-301 was an international, phase III, randomised, double-blind, placebo-controlled trial for patients with mCRPC post-docetaxel (clinicaltrials.gov: NCT00638690). Patients received oral abiraterone acetate (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone (5 mg twice daily), both regimens taken continuously on 4-weekly cycles. This study was approved by the review boards at all participating institutions and was conducted according to the principles set forth in
Patient characteristics
A total of 797 patients were randomised to abiraterone and 398 to prednisone. The median treatment duration was 7.4 and 3.6 months, respectively [11]. Median duration of follow-up for the overall study population was 20.2 months [11]. Patient compliance with the FACT-P questionnaire was high. The cumulative amount of available data, excluding deaths and study dropouts, in the updated analysis was 91.3% at cycle 28 (at that time point, only 326 (9%) of a total of 3752 possible assessments were not
Discussion
These results indicate that treatment with abiraterone resulted in a clinically meaningful improvement in patient-reported HRQoL. A larger proportion of patients taking abiraterone than prednisone experienced improvements in all of the FACT-P measures, with the exception of the SFWB subscale. Abiraterone also significantly reduced time to improvement in the PWB subscale and the TOI and significantly delayed deterioration in overall FACT-P and all subscales other than SFWB. Results from two
Authors’ contributions
Study conception and design: Howard I. Scher, Johann S. de Bono, Arturo Molina, Christopher M. Haqq, Thian Kheoh and Yanni Hao.
Collection and assembly of data: Stephen Harland, John Staffurth, Cora N. Sternberg, Arturo Molina, Thian Kheoh, Howard I. Scher, Karim Fizazi, Christopher J. Logothetis and Johann S. de Bono.
Data analysis and interpretation: Stephen Harland, Arturo Molina, Dennis D. Gagnon, Margaret Rothman, Yanni Hao, Thian Kheoh, Christopher M. Haqq and David Cella.
Figures: Yanni
Conflict of interest statement
Stephen Harland has received travel support from Janssen R&D and has served as a consultant to Sanofi-Aventis.
John Staffurth has received honoraria from and served as a consultant to Janssen R&D and holds stock in Johnson & Johnson.
Arturo Molina is a full-time employee of Janssen R&D and holds stock in Johnson & Johnson.
Yanni Hao was a full-time employee of Janssen Global Services at the time the study was conducted and holds stock in Johnson & Johnson.
Dennis D. Gagnon was a full-time employee
Acknowledgements
The authors would like to thank Margaret Rothman (Janssen Global Services) for her contributions to these analyses and critical review of this manuscript. This trial was funded by Janssen Research & Development (formerly Ortho Biotech Research and Development, a unit of Cougar Biotechnology). Dominik Wolf of PAREXEL provided writing assistance, which was funded by Janssen Global Services. This project was supported by researchers at the National Institute for Health Research University College
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Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial
2022, The Lancet OncologyCitation Excerpt :FACT-P compliance declined more quickly over time in the control group than in the olaparib group, and FACT-P compliance was generally lower than for BPI-SF. FACT-P overall compliance rates in this study (60% in the olaparib group and 53% in the control group) are lower than those reported in other relevant studies: COU-AA-302 (>95%)18 and COU-AA-301 (>91%)19 trials, in which patients with metastatic castration-resistant prostate cancer were treated with abiraterone. Patient crossover might partly explain the perceived lower compliance over time in the control group compared with the olaparib group for both BPI-SF and FACT-P because patient-reported outcome data were analysed only until a subsequent anti-cancer therapy was initiated.
Health-related Quality of Life in Patients with Advanced Prostate Cancer: A Systematic Review
2021, European Urology FocusCitation Excerpt :For both studies, HRQOL has been reported. Harland et al [24] analyzed HRQOL outcomes of 1395 patients using the FACT-P questionnaire. The authors found significant improvements in FACT-P total scores in 48% of patients receiving abiraterone acetate in combination with 10 mg prednisone daily versus 32% receiving placebo (p < 0.0001).
Cognition and depression effects of androgen receptor axis-targeted drugs in men with prostate cancer: A systematic review
2021, Journal of Geriatric OncologyCitation Excerpt :Thiery-Vuillemin found that cognitive functioning over 12 months based on FACT-Cog caregiver responses and EORTC-QLQ-C30 were statistically improved (odds ratio = 0.31; 95% CI: 0.14; 0.70; p = 0.005) and favored abiraterone over enzalutamide, respectively [38]. Eleven of fourteen studies assessed changes in depressive symptoms based on the FACT-P emotional wellbeing subscale but reported findings differently [29–33,36,39–43] (Table 4). Harland showed that abiraterone delayed median time to emotional wellbeing deterioration by 198 days compared to prednisone [29].
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Data presented in part at the European Multidisciplinary Cancer Congress, 2011, September 23–27, 2011, Stockholm, Sweden.
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Trial registration number: clinicaltrials.gov: NCT00638690.
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Co-senior author.