The PROSPER trial (NCT02003924) showed a clinically and statistically significant improvement in metastasis-free survival (HR 0.292 [95% CI 0.241, 0.352], p < 0.0001) with enzalutamide (ENZ; n = 933) versus placebo (PBO; n = 468) in asymptomatic men with nmCRPC and prostate-specific antigen doubling time ≤10 months. All men without prior orchiectomy continued androgen deprivation therapy. We assessed the impact of ENZ on prostate cancer symptoms (PCS) and health-related quality of life (HRQoL).
PCS and HRQoL were assessed at baseline (BL) and subsequently every 16 weeks, using the EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) and the EuroQol 5-domain 5-level (EQ-5D-5L). Clinically meaningful symptom worsening in PCS scores was defined using thresholds derived as 1/2 standard deviation at BL. Clinically meaningful deterioration in EQ-5D-5L visual analogue scale was defined using the pre-established threshold of 7. Time to first confirmed (at two consecutive visits) and unconfirmed (one visit) deterioration in QLQ-PR25 and EQ-5D-5L scores were assessed using Kaplan-Meier estimates and Cox models.
Completion rates were high for patients (pts) remaining on study (>85% for all visits). BL scores were similar between arms and showed low symptom burden (including urinary and bowel symptoms) and high HRQoL. The proportion of pts reporting either no change or improvement in HRQoL and PCS scores at week 49 was higher with ENZ (67 − 87%) than PBO (62 − 81%). Over the course of treatment, ENZ significantly delayed worsening of symptoms including urinary and bowel symptoms/function (Table). In contrast, ENZ significantly increased the risk of worsening of hormonal treatment related symptoms compared to PBO (Table).Table: 807P
|Baseline scores||Time to deterioration or symptom worsening|
|Instrument/scale||ENZ (n = 933)||PBO (n = 468)||Confirmed||Unconfirmed|
|n||Mean (SD)||n||Mean (SD)||Hazard ratio (95% CI)||Hazard ratio (95% CI)|
|PRAID*||144||20.37 (27.91)||67||24.38 (33.63)||NE||NE|
|PRBOW*||884||5.14 (8.39)||439||4.65 (7.70)||0.72 (0.59, 0.89)‡||0.80 (0.67, 0.95)‡|
|PRHTR*||884||14.92 (12.50)||439||15.79 (13.30)||1.29 (1.02, 1.63)‡||1.30 (1.08, 1.59)‡|
|PRSAC†||884||11.86 (20.05)||439||11.77 (20.63)||0.98 (0.77, 1.24)||1.04 (0.83, 1.31)|
|PRSFU†||49||53.40 (23.44)||24||48.26 (26.35)||NE||NE|
|PRURI*||884||20.69 (17.55)||439||20.02 (17.68)||0.58 (0.46, 0.72)‡||0.72 (0.60, 0.87)‡|
|EQ-VAS†||884||76.17 (16.92)||439||77.53 (15.97)||0.75 (0.63, 0.90)‡||0.83 (0.71, 0.97)‡|
Higher scores represent higher level of symptoms/more pain; †Higher scores represent higher level of functioning/better quality of life;‡
Statistically significant at 0.05. Results for the EORTC-QLQ-PR25 PRSFU and PRAID were not estimated because of the low sample size and small number of events. CI=confidence interval; ENZ=enzalutamide; EQ-5D-5L=EuroQol 5-domain 5-level questionnaire; EQ-VAS=EuroQol visual analogue scale; NE=not estimated; PBO=placebo; PRAID=incontinence aids; PRBOW=bowel symptoms/function; PRHTR=hormonal treatment-related symptoms; PRSAC=sexual activity; PRSFU=sexual functioning; PRURI=urinary symptoms and problems; QLQ-PR25=EORTC Quality of Life Questionnaire-Prostate 25; SD=standard deviation.
In addition to delayed disease progression in the PROSPER trial, ENZ prolonged urinary and bowel symptom control and delayed decline in HRQoL scores versus PBO.
Clinical trial identification
Legal entity responsible for the study
Astellas Pharma Inc and Pfizer Inc.
This study was funded by Astellas Pharma Inc and Pfizer Inc, the co-developers of enzalutamide.
Editorial assistance was provided by Lauren Smith from Complete HealthVizion, funded by Astellas Pharma Inc and Pfizer Inc, the co-developers of enzalutamide.
B. Tombal: Personal fees: Astellas, during the conduct of the study; Grants: Bayer, Janssen, Sanofi, Ferring; Personal fees: Bayer, Janssen, Sanofi, Ferring, Amgen; Non-financial support: Ferring, outside the submitted work. M. Hussain: Other: Genentech/Roche, Abbvie, Bayer, Onclive, Pfizer, PCCTC, AstraZeneca, outside the submitted work; Patent pending: Systems and methods for tissue imaging, Method of treating cancer, Dual inhibition of MET and VEGF; Applicant/Proprietor Exelexis, Inc. D. Penson: Grants, personal fees: Astellas, Medivation, during the conduct of the study; Grants, personal fees: Dendreon, outside the submitted work. G. Attard: Personal fees, non-financial support: Astellas, Medivation, Pfizer, during the conduct of the study; Personal fees: Janssen-Cilag, Veridex, Takeda Sanofi-Aventis Janssen, Roche, Ventana Millenium Pharmaceuticals, Abbott Laboratories, Essa Pharmaceuticals, Bayer Healthcare Pharmaceuticals; Non-financial support: Roche/Ventana, Abbott Laboratories, Essa Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Janssen; Grants: Janssen; AstraZeneca, Arno Therapeutics, Innocrin Pharma; Other: The Institute of Cancer Research (ICR), outside the submitted work. C.N. Sternberg: Oher: Bristol-Myers Squibb, Novartis, Janssen, Bayer, Eisai, MSD, Lilly, Clovis Oncology, Ferring, Pfizer, Astellas Pharma, Sanofi, Ipsen, AstraZeneca, outside the submitted work. D. Phung: Other from Astellas, outside the submitted work. R. Morlock: Personal fees: Astellas, during the conduct of the study; Personal fees: Abbot Medical Optics, Ironwood, Genentech, outside the submitted work. K. Modelska: Other: Pfizer, outside the submitted work. K. Ramaswamy: Other: PfizerInc, during the conduct of the study; Other: Johnson & Johnson, outside the submitted work. C. Ivanescu: Employee: QuintilesIMS, funding statistical analyses (for this work under consultancy contract): Astellas. F. Saad: Grants, personal fees: Astellas, Janssen, during the conduct of the study; Grants, personal fees: Sanofi, Bayer, outside the submitted work.