Tombal B, et al. - Researchers reported the patient-reported outcomes after enzalutamide treatment in patients with non-metastatic, castration-resistant prostate cancer in the PROSPER trial, in which, enzalutamide significantly improved metastasis-free survival in these patients. Longer metastasis-free survival was observed in patients treated with enzalutamide vs placebo. Enzalutamide also maintained low pain levels and prostate cancer symptom burden and high health-related quality of life. Enzalutamide vs placebo was clinically beneficial as it delayed pain progression, symptom worsening, and decrease in functional status. They recommended discussing enzalutamide, as a treatment option, with patients presenting with high-risk, non- metastatic, castration-resistant prostate cancer.

Methods

• Including patients aged 18 years or older with non-metastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of up to 10 months, a randomised, double-blind, placebo-controlled, phase 3 PROSPER trial was conducted at 254 study sites worldwide.
• Using randomisation stratified by prostate-specific antigen doubling time and baseline use of a bone-targeting agent, the participants were randomly assigned (2:1) via an interactive voice web recognition system to receive oral enzalutamide (160 mg per day) or placebo.  
• Metastasis-free survival, reported elsewhere, was the primary endpoint.
• Pain progression (assessed by the Brief Pain Inventory Short Form [BPI-SF] questionnaire) and health-related quality of life (assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-PR25], the EuroQoL 5-Dimensions 5-Levels health questionnaire visual analogue scale [EQ-5D-FL, EQ-VAS], and the Functional Assessment of Cancer Therapy-Prostate [FACT-P] questionnaires) were the secondary efficacy endpoints, reported here.
• Questionnaires were administered and were asked to complete at baseline, week 17, and every 16 weeks thereafter until treatment discontinuation.
• Clinically meaningful changes were detected using predefined questionnaire thresholds.
• Enrolment for PROSPER is complete and follow-up continues.

Results

• Enrollment of 1401 patients and random assignment to enzalutamide (n=933) or placebo (n=468) was done between Nov 26, 2013, and June 28, 2017.
• The enzalutamide group and the placebo group was followed for median duration of 18·5 months (IQR 10·7–29·2) and 15·1 months (7·4–25·9), respectively.
• At baseline, similar patient-reported outcome scores were found between groups.
• Regarding FACT-P social and family wellbeing, enzalutamide vs placebo was favoured by changes in least squares mean from baseline to week 97 (0·30 [95% CI −0·25 to 0·85] vs −0·64 [−1·51 to 0·24]; difference 0·94 [95% CI 0·02 to 1·85]; p=0·045) and these changes disfavoured enzalutamide vs placebo for EORTC QLQ-PR25 hormonal treatment-related symptoms (1·55 [0·26 to 2·83) vs −1·83 [−3·86 to 0·20]; difference 3·38 [1·24 to 5·51]; p=0·0020); neither of these changes were clinically meaningful.
• With respect to changes from baseline to week 97 in any other patient-reported outcome score, no remarkable differences were observed between treatments.
• With enzalutamide vs placebo, longer time to clinically meaningful pain progression as assessed by BPI-SF pain severity was noted (median 36·83 months, [95% CI 34·69 to not reached [NR] vs NR; hazard ratio [HR] 0·75 [95% CI 0·57 to 0·97]; p=0·028); no significant difference for BPI-SF item 3 or pain interference was observed.
• Enzalutamide vs placebo offered longer time to clinically meaningful symptom worsening for EORTC QLQ-PR25 urinary symptoms (median 36·86 months [95% CI 33·35 to NR] vs 25·86 [18·53 to 29·47]; HR 0·58 [95% CI 0·46 to 0·72]; p<0·0001) and bowel symptoms (33·15 [29·50 to NR]vs 25·89 [18·43 to 29·67]; 0·72 [0·59 to 0·89]; p=0·0018), and clinically meaningful health-related quality of life as assessed by FACT-P total score (22·11 [18·63 to 25·86] vs 18·43 [14·85–19·35]; 0·83 [0·69 to 0·99]; p=0·037), emotional wellbeing (36·73 [33·12 to 38·21] vs 29·47 [22·18 to 33·15]; 0·69 [0·55 to 0·86]; p=0·0008), and prostate cancer subscale (18·43 [14·85 to 18·66] vs 14·69 [11·07 to 16·20]; 0·79 [0·67 to 0·93]; p=0·0042), although no marked difference was observed for other FACT-P scores.
• Enzalutamide vs placebo provided shorter time to clinically meaningful deterioration in EORTC QLQ-PR25 hormonal treatment-related symptoms (median 33·15 months [95% CI 29·60 to NR] vs 36·83 [29·47 to NR]; HR 1·29 [95% CI 1·02 to 1·63]; p=0·035).
• For enzalutamide vs for placebo, a significantly longer time to deterioration of EQ-VAS was reported (median 22·11 months [95% CI 18·46 to 25·66] vs 14·75 [11·07 to 18·17]; HR 0·75 [95% CI 0·63 to 0·90]; p=0·0013).