Elsevier

European Journal of Cancer

Volume 49, Issue 17, November 2013, Pages 3648-3657
European Journal of Cancer

Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy,☆☆

https://doi.org/10.1016/j.ejca.2013.07.144Get rights and content

Abstract

Background

In a recent randomised, double-blind, phase III clinical trial among 1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly prolong overall survival compared with prednisone alone. Here we report on the impact of abiraterone therapy on the health-related quality of life (HRQoL) observed during this trial, assessed using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.

Methods

All analyses were conducted using prespecified criteria for clinically meaningful improvement and deterioration in FACT-P total score as well as subscale scores; all respective thresholds were defined using an accepted methodology. Improvement was assessed only in patients with clinically significant functional status impairment at baseline.

Results

Significant improvements in the FACT-P total score were observed in 48% of patients receiving abiraterone versus 32% of patients receiving prednisone (p < 0.0001). Also, the median time to deterioration in FACT-P total score was longer (p < 0.0001) in patients receiving abiraterone (59.9 weeks versus 36.1 weeks). Similar differences were observed in all FACT-P subscales, with the exception of the social/family well-being domain. Median time to improvement in the physical well-being domain and the trial outcome index was significantly shorter (p < 0.01) with abiraterone when compared with the prednisone arm.

Conclusions

The previously demonstrated survival benefit for abiraterone is accompanied by improvements in patient-reported HRQoL and a significant delay in HRQoL deterioration when compared with prednisone.

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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    Data presented in part at the European Multidisciplinary Cancer Congress, 2011, September 23–27, 2011, Stockholm, Sweden.

    ☆☆

    Trial registration number: clinicaltrials.gov: NCT00638690.

    l

    Co-senior author.

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