Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial

Abstract

Background In the phase 3, double-blind, placebo-controlled PROSPER trial of patients with non-metastatic castration-resistant prostate cancer, enzalutamide significantly improved metastasis-free survival (primary endpoint). Here, we report the results of patient-reported outcome (PRO) measures of this study. Methods Patients ≥18 years of age with non-metastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of ≤10 months were randomised (2:1) via interactive voice/web recognition system to receive enzalutamide (160 mg/day) or placebo. Randomisation was stratified by prostate-specific-antigen-doubling time (<6 months vs ≥6 months) and baseline use of a bone-targeting agent (yes or no). The primary endpoint was metastasis-free survival (MFS), reported elsewhere. Exploratory endpoints, reported here, included pain progression and health-related quality of life (HRQoL), assessed by the Brief Pain Inventory Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25), the Functional Assessment of Cancer Therapy-Prostate (FACT-P), and the EuroQoL 5-Dimensions 5-Levels health questionnaire visual analogue scale (EQ-VAS). Patients completed questionnaires at baseline, Week 17, and every 16 weeks thereafter during treatment. Pre-defined questionnaire thresholds were used to identify clinically meaningful changes. Enrollment for PROSPER is complete and follow-up continues. This trial is registered with ClinicalTrials.gov (NCT02003924). Findings Patients were enrolled from 26 November 2013 to 28 June 2017. Median followup time for all patients was 18•5 months (interquartile range [IQR] 10•7-29•2 months) in the enzalutamide group and 15•1 months (IQR 7•4-25•9 months) in the placebo group. Patients randomised to receive enzalutamide or placebo had similar baseline PRO scores. Changes in 6 Further analyses are needed to determine potential associations between pain, HRQoL, and disease progression in non-metastatic castration-resistant prostate cancer. Implications of all the available evidence As patients with non-metastatic castration-resistant prostate cancer generally have low levels of pre-treatment pain and favourable HRQoL compared to patients with advanced disease, treatments should aim to improve clinical outcomes while maintaining pain control and HRQoL. The demonstrated efficacy, tolerability, and HRQoL profile suggest that enzalutamide represents a treatment option for patients with non-metastatic castrationresistant prostate cancer. PROSPER patient recruitment sites, principal investigators and patients recruited by site* Country Site # Study centre Principal investigator # patients randomised Denmark 421 Herlev Hospital Per Rathenborg

Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

“…Patient-reported outcomes from PROSPER indicate that enzalutamide delayed pain progression, symptom worsening, and decrease in functional status compared with placebo. 194 The FDA expanded approval for enzalutamide to include men with nonmetastatic CRPC on July 13, 2018, 188 and the panel believes that patients with M0 CRPC can be offered enzalutamide if PSADT is #10 months (category 1).…”

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

“…Some PCa patients develop castration-resistant prostate cancer and later develop metastases. Few treatments are approved, like enzalutamide, that delay the progression of the illness while maintaining a good quality of life [8]. However, the resistance to therapy and risk of recurrence has led to the search for new effective anticancer compounds, including those from medicinal plants [9].…”

Matching-Adjusted Indirect Comparison of Health-Related Quality of Life and Adverse Events of Apalutamide Versus Enzalutamide in Non-Metastatic Castration-Resistant Prostate Cancer

“…When evaluating LS mean changes during follow-up versus baseline, a deterioration of HRQoL was numerically more apparent in the ADT arm than in the apalutamide arm. In PROSPER, discrepancies in the time to FACT-P deterioration exist between the unconfirmed and confirmed (i.e., deterioration confirmed at the next consecutive visit) analyses [1,24]. In the confirmed analysis, a significantly less rapid deterioration was observed in the enzalutamide arm compared with the ADT arm [24].…”

“…In PROSPER, discrepancies in the time to FACT-P deterioration exist between the unconfirmed and confirmed (i.e., deterioration confirmed at the next consecutive visit) analyses [1,24]. In the confirmed analysis, a significantly less rapid deterioration was observed in the enzalutamide arm compared with the ADT arm [24]. In terms of the LS mean changes in the FACT-P score during follow-up versus baseline, a numerical but not statistical advantage was observed for the enzalutamide arm in PROSPER [24].…”

“…In SPARTAN, a least squares (LS) mean change from baseline showed an HRQoL deterioration that was numerically more apparent in the ADT arm than in the apalutamide arm [23]. In PROSPER, Tombal et al reported that HRQoL deteriorated significantly less rapidly in the enzalutamide arm than in the ADT arm [24]. However, HRQoL outcomes have to date not been compared between apalutamide and enzalutamide.…”