Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial

Nancy Devlin, Michael Herdman, Marco Pavesi, De Phung, Shevani Naidoo, Tomasz M Beer, Bertrand Tombal, Yohann Loriot, Cristina Ivanescu, Teresa Parli, Mark Balk, Stefan Holmstrom, Nancy Devlin, Michael Herdman, Marco Pavesi, De Phung, Shevani Naidoo, Tomasz M Beer, Bertrand Tombal, Yohann Loriot, Cristina Ivanescu, Teresa Parli, Mark Balk, Stefan Holmstrom

Abstract

Background: The effect of enzalutamide on health-related quality of life (HRQoL) in the PREVAIL trial in chemotherapy-naïve men with metastatic castration-resistant prostate cancer was analyzed using the generic EQ-5D instrument.

Methods: Patients received oral enzalutamide 160 mg/day (n = 872) or placebo (n = 845). EQ-5D index and EQ-5D visual analogue scale (EQ-5D VAS) scores were evaluated at baseline, week 13, and every 12 weeks until week 61 due to sample size reduction thereafter. Changes on individual dimensions were assessed, and Paretian Classification of Health Change (PCHC) and time-to-event analyses were conducted.

Results: With enzalutamide, EQ-5D index and EQ-5D VAS scores declined more slowly versus placebo and time to diverge from full health was prolonged. Average decline in EQ-5D index (-0.042 vs. -0.070; P < .0001) and EQ-5D VAS (-1.3 vs. -4.4; P < .0001) was significantly smaller with enzalutamide. There were significant (P < .05) between-group differences favoring enzalutamide in Pain/Discomfort to week 37, Anxiety/Depression at week 13, and Usual Activities at week 25, but no significant differences for Mobility and Self-care. The PCHC analysis showed more enzalutamide patients reporting improvement than placebo patients at weeks 13, 25, and 49 (all P < .05) and week 37 (P = .0512). Enzalutamide was superior (P ≤ .0003) to placebo for time to diverge from full health and time to first deterioration on Pain/Discomfort and Anxiety/Depression dimensions.

Conclusions: This in-depth post hoc analysis showed that enzalutamide delayed HRQoL deterioration and had beneficial effects on several HRQoL domains, including Pain/Discomfort and the proportion of patients in full health, compared with placebo, and may help to support future analyses of this type.

Trial registration: NCT01212991.

Keywords: Enzalutamide; Eq-5D; Metastatic castration-resistant prostate cancer; Quality of life.

Figures

Fig. 1
Fig. 1
Number and proportion of patients in full health (EQ-5D state 11111) at each study visit, by study arm

References

    1. Sandblom G, Carlsson P, Sennfält K, Varenhorst E. A population-based study of pain and quality of life during the year before death in men with prostate cancer. Br J Cancer. 2004;90:1163–1168. doi: 10.1038/sj.bjc.6601654.
    1. Sullivan PW, Mulani PM, Fishman M, Sleep D. Quality of life findings from a multicenter, multinational, observational study of patients with metastatic hormone-refractory prostate cancer. Qual Life Res. 2007;16:571–575. doi: 10.1007/s11136-006-9156-2.
    1. Payne H, Pearcy R. Symptoms and health-related quality of life in castration-resistant prostate cancer: the patient's perspective. J Mens Health. 2012;9:9–16. doi: 10.1016/j.jomh.2011.11.002.
    1. Merseburger AS, Bellmunt J, Jenkins C, et al. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 2013;18:558–567. doi: 10.1634/theoncologist.2012-0478.
    1. Suzman DL, Antonarakis ES. Castration-resistant prostate cancer: latest evidence and therapeutic implications. Ther Adv Med Oncol. 2014;6:167–179. doi: 10.1177/1758834014529176.
    1. Scher HI, Halabi S, Tannick I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate cancer clinical trials working group. J Clin Oncol. 2008;26:1148–1159. doi: 10.1200/JCO.2007.12.4487.
    1. Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ. Measuring quality of life in men with prostate cancer using the Functional assessment of cancer therapy-prostate instrument. Urology. 1997;50:920–928. doi: 10.1016/S0090-4295(97)00459-7.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–366. doi: 10.1093/jnci/85.5.365.
    1. EuroQol Group EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199–208. doi: 10.1016/0168-8510(90)90421-9.
    1. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol group. Ann Med. 2001;33:337–343. doi: 10.3109/07853890109002087.
    1. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–790. doi: 10.1126/science.1168175.
    1. Hu R, Denmeade SR, Luo J. Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer. Expert Rev Endocrinol Metab. 2010;5:753–764. doi: 10.1586/eem.10.49.
    1. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–1197. doi: 10.1056/NEJMoa1207506.
    1. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–433. doi: 10.1056/NEJMoa1405095.
    1. Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S, et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015;16:509–521. doi: 10.1016/S1470-2045(15)70113-0.
    1. Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014;15:1147–1156. doi: 10.1016/S1470-2045(14)70303-1.
    1. Devlin NJ, Parkin D, Browne J. Patient-reported outcome measures in the NHS: new methods for analysing and reporting EQ-5D data. Health Econ. 2010;19:886–905. doi: 10.1002/hec.1608.
    1. EuroQol 2015. EQ-5D-3L User Guide. . Accessed 13 Jan 2016.
    1. Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes. 2007;5:70. doi: 10.1186/1477-7525-5-70.
    1. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35:1095–1108. doi: 10.1097/00005650-199711000-00002.
    1. Sullivan PW, Nelson JB, Mulani PM, Sleep D. Quality of life as a potential predictor for morbidity and mortality in patients with metastatic hormone-refractory prostate cancer. Qual Life Res. 2006;15:1297–1306. doi: 10.1007/s11136-006-0003-2.
    1. Cella D, Ivanescu C, Holmstrom S, Bui CN, Spalding J, Fizazi K. Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial. Ann Oncol. 2015;26:179–185. doi: 10.1093/annonc/mdu510.
    1. Basch E, Autio K, Ryan CJ, Mulders P, Shore N, Kheoh T, et al. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial. Lancet Oncol. 2013;14:1193–1199. doi: 10.1016/S1470-2045(13)70424-8.
    1. Gater A, Abetz-Webb L, Battersby C, Parasuraman B, McIntosh S, Nathan F, et al. Pain in castration-resistant prostate cancer with bone metastases: a qualitative study. Health Qual Life Outcomes. 2011;9:88. doi: 10.1186/1477-7525-9-88.
    1. Armstrong AJ, Garrett-Mayer E, Yang Y-CO, Carducci MA, Tannock I, de Wit R, et al. Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2007;25:3965–3970. doi: 10.1200/JCO.2007.11.4769.
    1. Halabi S, Vogelzang NJ, Kornblith AB, Ou SS, Kantoff PW, Dawson NA, et al. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol. 2008;26:2544–2549. doi: 10.1200/JCO.2007.15.0367.
    1. Deandrea S, Montanari M, Moja M, Apolone G. Prevalence of undertreatment in cancer pain. A review of published literature. Ann Oncol. 2008;19:1985–1991. doi: 10.1093/annonc/mdn419.
    1. Apolone G, Corli O, Caraceni A, Negri E, Deandrea S, Montanari M, et al. Pattern and quality of care of cancer pain management. Results from the cancer pain outcome research study group. Br J Cancer. 2009;100:1566–1574. doi: 10.1038/sj.bjc.6605053.
    1. Watts S, Leydon G, Birch B, Prescott P, Lai L, Eardley S, et al. Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates. BMJ Open. 2014;4:e003901. doi: 10.1136/bmjopen-2013-003901.
    1. Gerrits MM, van Marwijk HW, van Oppen P, van der Horst H, Penninx BW. Longitudinal association between pain, and depression and anxiety over four years. J Psychosom Res. 2015;78:64–70. doi: 10.1016/j.jpsychores.2014.10.011.
    1. Ko HJ, Seo SJ, Youn CH, Kim HM, Chung SE. The association between pain and depression, anxiety, and cognitive function among advanced cancer patients in the hospice ward. Korean J Fam Med. 2013;34:347–356. doi: 10.4082/kjfm.2013.34.5.347.
    1. Skaltsa K, Longworth L, Ivanescu C, Phung D, Holmstrom S. Mapping the FACT-P to the preference-based EQ-5D questionnaire in metastatic castration-resistant prostate cancer. Value Health. 2014;17:238–244. doi: 10.1016/j.jval.2013.12.005.
    1. Wolff JM, Donatz V, Klier J, Erhardt W, Dass RN, Geiges G. Quality of life among German patients with metastatic castration-resistant prostate cancer [abstract] Value Health. 2012;15:A431. doi: 10.1016/j.jval.2012.08.2160.
    1. Wu EQ, Mulani P, Farrell MH, Sleep D. Mapping FACT-P and EORTC QLQ-C30 to patient health status measured by EQ-5D in metastatic hormone-refractory prostate cancer patients. Value Health. 2007;10:408–414. doi: 10.1111/j.1524-4733.2007.00195.x.
    1. Feng Y, Devlin N, Herdman M. Assessing the health of the general population in England: how do the three- and five-level versions of EQ-5D compare? Health Qual Life Outcomes. 2015;13:171. doi: 10.1186/s12955-015-0356-8.

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