Worst Itch Numeric Rating Scale for Prurigo Nodularis: A Secondary Analysis of 2 Randomized Clinical Trials.

Importance: Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN. Objective: To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN. Design, Setting, and Participants: In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2. Exposures: Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks. Main outcomes and measures: WI-NRS score at specified time points up to 24 weeks after randomization. Results: A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods. Conclusion and Relevance: This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN. Trial Registration: NCT04183335 (PRIME) and NCT04202679 (PRIME2).

The Relationship Between Health-Related Quality of Life and Overall Survival in Patients With Advanced Renal Cell Carcinoma in CheckMate 214.

BACKGROUND: In CheckMate 214 (median follow-up, 25.2 months), nivolumab plus ipilimumab yielded greater overall survival (OS) benefit than sunitinib in patients with intermediate-/poor-risk advanced renal cell carcinoma (aRCC). Health-related quality of life (HRQoL) assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19) was also more favorable for the nivolumab plus ipilimumab group than the sunitinib group. We investigated whether HRQoL scores can predict OS of patients with 5 years follow-up in CheckMate 214. PATIENTS AND METHODS: CheckMate 214 was an open-label, phase III trial in previously untreated aRCC (N = 1096). Patients with intermediate-/poor-risk disease (International mRCC Database Consortium prognostic score ≥ 1; n = 847) were randomized to either nivolumab plus ipilimumab or sunitinib monotherapy. Pooled data for OS and FKSI-19 total and subscales (disease-related symptoms [DRS], DRS-physical [DRS-P], and function/well-being [FWB]) were analyzed. Relationships between HRQoL and OS were assessed using Cox proportional hazard models with baseline and longitudinal scores. Associations between HRQoL changes and OS were assessed by landmark analyses. RESULTS: Patients with higher FKSI-19 total and subscale scores at baseline had longer OS than patients with lower scores (HR ≤ 0.834; P < .0001). Longitudinal models indicated stronger associations between HRQoL and OS (HR ≤ 0.69; P < .001 for each). At 3 months after randomization, patients with stable/improved HRQoL versus baseline had longer median OS than patients with worsened/unobserved HRQoL versus baseline (55.9 and 26.0 months, respectively; HR = 0.56; 95% CI, 0.46-0.67; P < .0001). Results at 6-, 9-, and 12-month landmarks were consistent with these findings. CONCLUSION: In aRCC, patient-reported outcomes are important for HRQoL and prognostic evaluation. CLINICALTRIALS.GOV IDENTIFIER: NCT02231749; https://clinicaltrials.gov/ct2/show/NCT02231749.

Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study.

Background and Objectives: The Pompe Disease Symptom Scale (PDSS) and Impact Scale (PDIS) were created to measure the severity of symptoms and functional limitations experienced by patients with late-onset Pompe disease (LOPD). The objectives of this analysis were to establish a scoring algorithm and to examine the reliability, validity, and responsiveness of the measures using data from the COMET clinical trial. Methods: The COMET trial was a randomized, double-blind study comparing the efficacy and safety of avalglucosidase alfa and alglucosidase alfa in patients with LOPD aged 16-78 years at baseline. Adult participants (18 years or older) completed the PDSS and PDIS daily for 14 days at baseline and for 2 weeks before quarterly clinic visits for 1 year after randomization using an electronic diary. Data were pooled across treatment groups for the current analyses. Factor analysis and inter-item correlations were used to derive a scoring algorithm. Test-retest and internal consistency analyses examined the reliability of the measures. Correlations with criterion measures were used to evaluate validity and sensitivity to change. Anchor and distribution-based analyses were conducted to estimate thresholds for meaningful change. Results: Five multi-item domain scores were derived from the PDSS (Shortness of Breath, Overall Fatigue, Fatigue/Pain, Upper Extremity Weakness, Pain) and 2 from the PDIS (Mood, Difficulty Performing Activities). Internal consistency (Cronbach α > 0.90) and test-retest reliability (intraclass correlation >0.60) of the scores were supported. Cross-sectional and longitudinal correlations with the criterion measures generally supported the validity of the scores (r > 0.40). Within-patient meaningful change estimates ranging from 1.0 to 1.5 points were generated for the PDSS and PDIS domain scores. Discussion: The PDSS and PDIS are reliable and valid measures of LOPD symptoms and functional impacts. The measures can be used to evaluate burden of LOPD and effects of treatments in clinical trials, observational research, and clinical practice. Trial Registration Information: ClinicalTrials.gov identifier: NCT02782741.

Psychometric Validation and Meaningful Change Thresholds of the New Nasal Polyposis Symptom Diary.

OBJECTIVES: The Nasal Polyposis Symptom Diary (NPSD) is a novel and short patient-reported outcome (PRO) tool specifically developed to assess important and relevant symptoms reported by patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). We evaluated the psychometric properties of 4 predefined NPSD-derived scores intended to support symptom-improvement assessments of investigational therapies for inclusion in product labeling. METHODS: Five hundred eighteen patients with severe CRSwNP from a Phase III clinical trial (NCT03401229) completed the NPSD, comprising 11 items: 8 symptom-specific, 2 symptom-impact, and 1 optional medication-compliance. The psychometric characteristics of 3 single-item symptom scores (Nasal Blockage Score [NBS], Nasal Congestion Score [NCS], and Difficulty with Sense of Smell Score [DSS]) and a Total Symptom Score (TSS, summary of the 8 symptom-specific items) were evaluated for reliability, validity, and ability to detect change. Within-patient meaningful change thresholds (MCTs) were established using anchor- and distribution-based methods. Comparative PROs included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Patient Global Impression of Severity (PGI-S). RESULTS: The TSS exhibited strong internal consistency (Cronbach α = .88) and test-retest reliability (intraclass correlation coefficient >.80). Correlation between the TSS and SNOT-22 total score indicated good convergent validity (r = .70). All 4 NPSD scores demonstrated known-groups validity (significant differences among subgroups of patients with predetermined disease severity levels based on PGI-S categories) and were sensitive to detect change in patients' clinical status (significant differences among subgroups of patients with reported changes between 2 time-points in PGI-S and Patient Global Impression of Change scores). MCTs for improvement were established at 1.0 point for NBS, NCS, and DSS, and 4.0 points for TSS. CONCLUSION: These findings support the reliability, validity, and suitability of the 4 NPSD-derived scores for evaluating treatment effect on CRSwNP symptoms and their use in clinical trials with predetermined MCTs for improvement.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

BACKGROUND: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). METHODS: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. RESULTS: A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. CONCLUSION: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.

Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML.

Patient-reported outcomes (PROs) can inform treatment selection and assess treatment value in acute myeloid leukemia (AML). We evaluated PROs from the ADMIRAL trial (NCT02421939) in patients with FLT3-mutated relapsed/refractory (R/R) AML. PRO instruments consisted of Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), Functional Assessment of Chronic Illness Therapy-Dyspnea Short Form (FACIT-Dys SF), EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and leukemia treatment-specific symptom questionnaires. Clinically significant effects on fatigue were observed with gilteritinib during the first two treatment cycles. Shorter survival was associated with clinically significant worsening of BFI, FACT-Leu, FACIT-Dys SF, and EQ-5D-5L measures. Transplantation and transfusion independence in gilteritinib-arm patients were also associated with maintenance or improvement in PROs. Health-related quality of life remained stable in the gilteritinib arm. Hospitalization had a small but significant effect on patient-reported fatigue. Gilteritinib was associated with a favorable effect on fatigue and other PROs in patients with FLT3-mutated R/R AML.

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma.

BACKGROUND: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. OBJECTIVE: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. DESIGN, SETTING, AND PARTICIPANTS: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. INTERVENTION: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. RESULTS AND LIMITATIONS: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. CONCLUSIONS: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. PATIENT SUMMARY: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study.

BACKGROUND: In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants. METHODS: Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. RESULTS: In PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. CONCLUSIONS: Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Validation of the PRUCISION Instruments in Pediatric Patients with Progressive Familial Intrahepatic Cholestasis.

INTRODUCTION: Patients with cholestatic liver disease, including progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome, may have debilitating pruritus, and reducing pruritus is a key therapeutic goal. However, few instruments are available that adequately measure pruritus in pediatric patients with cholestatic liver disease. The objectives of the current study were to establish the measurement properties of the novel PRUCISION patient-reported outcome (PRO) and observer-reported outcome (ObsRO) instruments and to estimate a threshold for clinically meaningful change in pruritus score. METHODS: The PRO/ObsRO instruments are completed twice daily via electronic diary and include 5-point pictorial responses to assess pruritus. Sleep disturbance and tiredness were quantified using 5-point pictorial responses, yes/no responses, and numerical ratings. Data from PEDFIC 1 (NCT03566238), a phase 3 study evaluating odevixibat efficacy and safety in children with PFIC, were used to assess the psychometric properties of these instruments. Quantitative assessments included evaluation of test-retest reliability, determination of construct validity via convergent and known-group validity analyses, and characterization of sensitivity to change. A threshold for within-patient meaningful change from baseline to week 24 was determined using blinded data from PEDFIC 1 and distribution- and anchor-based analyses. RESULTS: Because the majority of patients in PEDFIC 1 were aged < 8 years (n = 52/62) and thus too young to complete the PRO instrument, which was intended for patients aged ≥ 8 years, the small sample size of patients who completed the PRO precluded a full psychometric analysis of the PRO instrument. The ObsRO was completed by a caregiver of every patient in PEDFIC 1. The ObsRO instrument had acceptable test-retest reliability based on intraclass correlation values (most > 0.75). Convergent validity analyses revealed moderate-to-strong correlations (r ≥ 0.3) between baseline ObsRO pruritus scores and baseline Global Impression of Symptoms (GIS) items. In known-groups validity analyses, there were significant differences between baseline groups defined by the GIS for ObsRO pruritus scores and for some sleep disturbance scores. Week 24 ObsRO scores were in the expected direction in groups defined by the Global Impression of Change scale (i.e., improved or not improved); many mean differences between these groups were significant. Sensitivity to change for the ObsRO PRUCISION instrument was also demonstrated by moderate-to-strong Pearson correlations between change from baseline to weeks 21-24 in ObsRO scores and GIS items (r ≥ 0.3). Based on these analyses, a within-patient change of -1.00 from baseline in ObsRO pruritus score was determined to be clinically meaningful. CONCLUSION: The PRUCISION ObsRO instrument is reliable, valid, and sensitive to change, supporting its use as a tool to measure pruritus and sleep disturbance in patients with PFIC and other pediatric cholestatic liver diseases.

Progressive familial intrahepatic cholestasis (PFIC) is a collection of liver diseases that typically affects very young children. A problematic symptom of PFIC is extremely itchy skin, or pruritus, that can keep patients and their families up at night. The PRUCISION questionnaire was developed to measure the severity of a patient's pruritus and sleep disturbance from the perspective of the patient's caregiver. The current study had two primary goals: (1) to assess whether PRUCISION could reliably measure these symptoms and detect changes over time relative to other established rating scales that assess related concepts, and (2) to identify what score change on PRUCISION could be considered clinically meaningful. To do this, data from a clinical study, called PEDFIC 1, in patients with PFIC were used: patient's scores on PRUCISION from their caregiver's perspective were compared with scores on other established scales, first before any treatment was given in PEDFIC 1, and then again after 24 weeks of treatment with a drug called odevixibat. In general, there was good agreement between PRUCISION scores and scores on other scales. For example, when PRUCISION scores indicated that symptoms improved, this tended to correlate with improvement on other measures. Additionally, these analyses indicated that if the PRUCISION score drops by 1 point or more, that can be considered a clinically important change. Overall, this study found that the caregiver-reported PRUCISION questionnaire is valid for assessing changes in pruritus and sleep symptoms in patients with PFIC, which may benefit patients as new treatments are developed.

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer.

BACKGROUND: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. METHODS: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1-16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. RESULTS: Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77-13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08-12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. CONCLUSIONS: Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.

The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups.

BACKGROUND: Enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in ARCHES (NCT02677896). While health-related quality of life (HRQoL) was generally maintained in the intent-to-treat population, we further analyzed patient-reported outcomes (PROs) in defined subgroups. METHODS: ARCHES was a randomized, double-blind, placebo-controlled, phase 3 study. Patients with mHSPC received enzalutamide (160 mg/day) plus ADT (n = 574) or placebo plus ADT (n = 576). Questionnaires, including the Functional Assessment of Cancer Therapy-Prostate, Brief Pain Inventory-Short Form, and EuroQol 5-Dimension, 5-Level (EQ-5D-5L), were completed at baseline, Week 13, and every 12 weeks until disease progression. PRO endpoints were time to first confirmed clinically meaningful deterioration (TTFCD) in HRQoL or pain. Subgroups included prognostic risk, pain/HRQoL, prior docetaxel, and local therapy (radical prostatectomy [RP] and/or radiotherapy [RT]). RESULTS: There were several between-treatment differences in TTFCD for pain and functioning/HRQoL PROs. Enzalutamide plus ADT delayed TTFCD for worst pain in the prior RT group (not reached vs. 14.06 months; hazard ratio [HR]: 0.56 [95% confidence interval: 0.34-0.94]) and pain interference in low-baseline-HRQoL group (19.32 vs. 11.20 months; HR: 0.64 [0.44-0.94]) versus placebo plus ADT. In prior/no prior RP, prior RT, prior local therapy, no prior docetaxel, mild baseline pain, and low-risk subgroups, TTFCD was delayed for the EQ-5D-5L visual analog scale. CONCLUSION: Enzalutamide plus ADT provides clinical benefits in defined patient subgroups versus ADT alone, while maintaining lack of pain and high HRQoL, with delayed deterioration in several HRQoL measures.

Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial.

BACKGROUND: In the CheckMate 9ER trial, patients with advanced renal cell carcinoma who received first-line nivolumab plus cabozantinib had significantly better progression-free survival compared with those given sunitinib. In this study, we aimed to describe the patient-reported outcome (PRO) results from CheckMate 9ER. METHODS: In this open-label, randomised, phase 3 trial done in 125 cancer centres, urology centres, and hospitals across 18 countries, patients aged 18 years or older with previously untreated advanced renal cell carcinoma with a clear-cell component, a Karnofsky performance status of 70% or more, and available tumour tissue were randomly assigned (1:1) via interactive response technology to nivolumab 240 mg intravenously every 2 weeks plus oral cabozantinib 40 mg per day, or oral sunitinib 50 mg per day monotherapy for 4 weeks in 6-week cycles. The primary endpoint of progression-free survival was reported previously. PROs were analysed as prespecified exploratory endpoints at common timepoints (at baseline and every 6 weeks) until week 115. Disease-related symptoms were evaluated using the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and global health status was assessed with the three-level EQ-5D (EQ-5D-3L) visual analogue scale (VAS) and UK utility index. PRO analyses were done in the intention-to-treat population. Change from baseline was assessed using mixed-model repeated measures. A time-to-deterioration analysis was done for first and confirmed deterioration events. This study is registered with ClinicalTrials.gov, NCT03141177, and is closed to recruitment. FINDINGS: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to nivolumab plus cabozantinib and 328 to sunitinib. Median follow-up was 23·5 months (IQR 21·0-26·5). At baseline, patients in both groups reported low symptom burden (FKSI-19 disease-related symptoms version 1 mean scores at baseline were 30·24 [SD 5·19] for the nivolumab plus cabozantinib group and 30·06 [5·03] for the sunitinib group). Change from baseline in PRO scores indicated that nivolumab plus cabozantinib was associated with more favourable outcomes versus sunitinib (treatment difference 2·38 [95% CI 1·20-3·56], nominal p<0·0001, effect size 0·33 [95% CI 0·17-0·50] for FKSI-19 total score; 1·33 [0·84-1·83], nominal p<0·0001, 0·45 [0·28-0·61] for FKSI-19 disease-related symptoms version 1; 3·48 [1·58-5·39], nominal p=0·0004, 0·30 [0·14-0·47] for EQ-5D-3L VAS; and 0·04 [0·01-0·07], nominal p=0·0036, 0·25 [0·08-0·41] for EQ-5D-3L UK utility index), reaching significance at most timepoints. Nivolumab plus cabozantinib was associated with decreased risk of clinically meaningful deterioration for FKSI-19 total score compared with sunitinib (first deterioration event hazard ratio 0·70 [95% CI 0·56-0·86], nominal p=0·0007; confirmed deterioration event 0·63 [0·50-0·80], nominal p=0·0001). INTERPRETATION: PROs were maintained or improved with nivolumab plus cabozantinib versus sunitinib. Compared with sunitinib, nivolumab plus cabozantinib significantly delayed time to deterioration of patient-reported outcome scores. These results suggest a benefit for nivolumab plus cabozantinib compared with sunitinib in the treatment of patients with advanced renal cell carcinoma. FUNDING: Bristol Myers Squibb.

Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.

BACKGROUND: Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)). METHODS: Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures. RESULTS: The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials. CONCLUSIONS: The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.

The Impact of Enzalutamide on the Prostate Cancer Patient Experience: A Summary Review of Health-Related Quality of Life across Pivotal Clinical Trials.

This review examines the impact of treatment with enzalutamide on health-related quality of life (HRQoL) in prostate cancer patients across the disease continuum based on pivotal clinical trials. We assessed the effect of enzalutamide on pain, symptom burden and overall HRQoL from randomized controlled trials. Patient experience was evaluated in men with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC) (pre-chemotherapy and post-chemotherapy). Patients across the disease continuum reported a generally positive status at baseline, with relatively low levels of pain and impairment due to cancer-related symptoms and high HRQoL. For patients with earlier-state prostate cancer, pain and symptom-related burden were low at study entry and remained so, regardless of whether patients received enzalutamide or control treatment. Patients with more advanced disease reported mitigation in pain and symptom burden while receiving treatment with enzalutamide. Enzalutamide was observed to slow deterioration of overall HRQoL most for patients with nmCRPC or mCRPC (statistical significance for between-group difference in median time to deterioration: mHSPC (confirmed) p = 0.2998; nmCRPC (confirmed) p = 0.0044; mCRPC (unconfirmed) p < 0.0001). Across the prostate cancer continuum, enzalutamide is well-tolerated and delays the negative impact that disease progression has on quality of life.

Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia.

PURPOSE: Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research. METHODS: The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318). RESULTS: Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach's coefficient α > 0.85 and McDonald's omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman's r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population. CONCLUSIONS: Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.

Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study.

BACKGROUND: In the ARCHES study in metastatic hormone-sensitive prostate cancer (mHSPC), enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) versus ADT alone. OBJECTIVE: To evaluate patient-reported outcomes (PROs) to week 73. DESIGN, SETTING, AND PARTICIPANTS: ARCHES (NCT02677896) was a randomised, double-blind, placebo-controlled, phase 3 study in mHSPC patients. INTERVENTION: Enzalutamide (160 mg/day) plus ADT or placebo plus ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PROs were assessed at baseline, week 13, and every 12 wk until disease progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate 25 (QLQ-PR25), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory Short Form, and EuroQoL 5-Dimensions, 5-Levels (EQ-5D-5 L) instruments. Endpoints included time to first (TTFD) and first confirmed (TTFCD) clinically meaningful deterioration (using predefined questionnaire thresholds) in health-related quality of life (HRQoL) and pain. RESULTS AND LIMITATIONS: A total of 1150 patients received ADT plus enzalutamide (n = 574) or placebo (n = 576). Baseline PRO scores indicated high HRQoL and low pain, which was generally maintained in both groups. There were no statistically significant (nominal p > 0.05) between-group differences that occurred in both TTFD and TTFCD together for QLQ-PR25 and FACT-P scores. Enzalutamide significantly delayed TTFD in worst pain (by ∼3 mo; nominal p = 0.032), pain severity (nominal p = 0.021), and EQ-5D-5 L visual analogue scale score (nominal p = 0.0070) versus placebo (not significant for confirmed deterioration for pain outcomes). Enzalutamide delays deterioration in several HRQoL subscales and pain severity in high-volume disease. CONCLUSIONS: Enzalutamide plus ADT enables men with mHSPC to maintain high-functioning HRQoL and low symptom burden. PATIENT SUMMARY: This study examined the effect on health-related quality of life and pain of adding enzalutamide or placebo to androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer. Addition of enzalutamide allowed patients to maintain their health-related quality of life.

Validity and performance of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) among advanced urothelial cancer patients.

PURPOSE: The recent increase in emerging novel therapies in the bladder cancer therapeutic area has increased the need for fit-for-purpose patient-reported outcome (PRO) measures for these patients. This study evaluates the psychometric properties of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) in 182 patients with advanced urothelial cancer (UC) and fills an important gap by demonstrating its validity for use in clinical trials. METHODS: Data were collected as part of a multicentre, open-label study of durvalumab in patients with inoperable or metastatic solid tumours. Psychometric properties evaluated include item and subscale characteristics (including correlation analysis), reliability (estimated using Cronbach's α), validity (by independent sample t test), responsiveness (using mixed models with repeated measures), and clinically meaningful changes using both anchor-based and distribution-based methods. RESULTS: One hundred and seventy-two patients completed the FACT-Bl questionnaire at baseline. Many individual items had floor or ceiling effects indicative of minimal symptoms and high functioning. The psychometric properties of the existing established scales were assessed and found to range from acceptable to very good. Internal consistency (most Cronbach's α coefficients range 0.66-0.85) and stability (test-retest reliability) generally exceeded standards for good reliability (most estimated intraclass correlations [ICCs] exceeded 0.70, although ICCs for some items [e.g. emotional well-being, ICC 0.58; social well-being, ICC 0.66] were lower than 0.70). Evidence for known-group validity of relevant FACT-Bl subscales and total score was demonstrated by significant differences between groups defined by baseline tumour burden and quality of life scores (difference of FACT-Bl total between low/high tumour burden groups 11.72 (p = 0.001); difference between low/high QoL scores groups 30.51 (p < 0.0001)). The FACT-Bl subscale and total scores were responsive to changes in bladder cancer symptom severity. Clinically meaningful changes in FACT-Bl scores were estimated. CONCLUSIONS: Results support the use of the FACT-Bl within this patient population in future clinical research.

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.

BACKGROUND: In the PROSPER trial, enzalutamide significantly improved metastasis-free survival in patients with non-metastatic, castration-resistant prostate cancer. Here, we report the results of patient-reported outcomes of this study. METHODS: In the randomised, double-blind, placebo-controlled, phase 3 PROSPER trial, done at 254 study sites worldwide, 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 were randomly assigned (2:1) via an interactive voice web recognition system to receive oral enzalutamide (160 mg per day) or placebo. Randomisation was stratified by prostate-specific antigen doubling time and baseline use of a bone-targeting agent. The primary endpoint was metastasis-free survival, reported elsewhere. Secondary efficacy endpoints, reported here, were 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). Patients completed questionnaires at baseline, week 17, and every 16 weeks thereafter until treatment discontinuation. We used predefined questionnaire thresholds to identify clinically meaningful changes. Enrolment for PROSPER is complete and follow-up continues. This trial is registered with ClinicalTrials.gov, number NCT02003924. FINDINGS: Between Nov 26, 2013, and June 28, 2017, 1401 patients were enrolled and randomly assigned to receive enzalutamide (n=933) or placebo (n=468). Median follow-up was 18·5 months (IQR 10·7-29·2) in the enzalutamide group and 15·1 months (7·4-25·9) in the placebo group. Patient-reported outcome scores at baseline were similar between groups. Changes in least squares mean from baseline to week 97 favoured enzalutamide versus placebo for FACT-P social and family wellbeing (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 disfavoured enzalutamide versus 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. No significant differences were observed between treatments for changes from baseline to week 97 in any other patient-reported outcome score. Time to clinically meaningful pain progression as assessed by BPI-SF pain severity was longer with enzalutamide than with placebo (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); there was no significant difference for BPI-SF item 3 or pain interference. Time to clinically meaningful symptom worsening was longer with enzalutamide than with placebo 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 there was no significant difference for other FACT-P scores. Time to clinically meaningful deterioration in EORTC QLQ-PR25 hormonal treatment-related symptoms was shorter with enzalutamide than with placebo (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). Time to deterioration of EQ-VAS was significantly longer for enzalutamide than for placebo (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). INTERPRETATION: Patients with non-metastatic, castration-resistant prostate cancer receiving enzalutamide had longer metastasis-free survival than did those who received placebo, while maintaining low pain levels and prostate cancer symptom burden and high health-related quality of life. Enzalutamide showed a clinical benefit by delaying pain progression, symptom worsening, and decrease in functional status, compared with placebo. These findings suggest that enzalutamide is a treatment option that should be discussed with patients presenting with high-risk, non- metastatic, castration-resistant prostate cancer. FUNDING: Astellas Pharma Inc, Medivation LLC (a Pfizer Company).

Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial.

BACKGROUND: In the ongoing phase 3, CheckMate 214 trial, nivolumab plus ipilimumab improved overall survival compared with sunitinib in patients with intermediate or poor risk, previously untreated, advanced renal cell carcinoma. We aimed to assess whether health-related quality of life (HRQoL) could be used to further describe the benefit-risk profile of nivolumab plus ipilimumab versus sunitinib. METHODS: In the phase 3, randomised, controlled, CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by risk status into favourable, intermediate, and poor risk subgroups and randomly assigned (1:1) to open-label nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg/day for 4 weeks of each 6-week cycle. Randomisation was done with a block size of four and stratified by risk status and geographical region. Patient-reported outcomes (PROs) were assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five dimensional three level (EQ-5D-3L) instruments. The coprimary endpoints of the trial, reported previously, were overall survival, progression-free survival, and the proportion of patients who had an objective response in those categorised as at intermediate or poor risk. PROs in all randomised participants were assessed as an exploratory endpoint; here we report this exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT02231749, and is ongoing but is now closed to recruitment. FINDINGS: Between Oct 16, 2014, and Feb 23, 2016, of 1390 patients screened, 1096 (79%) were randomly assigned to treatment, of whom 847 (77%) were at intermediate or poor risk and randomly assigned to nivolumab plus ipilimumab (n=425) or sunitinib (n=422). Median follow-up was 25·2 months (IQR 23·0-27·4). PROs were more favourable with nivolumab plus ipilimumab than sunitinib throughout the first 103 weeks after baseline, with mean change from baseline at week 103 for FKSI-19 total score being 4·00 (95% CI 1·91 to 6·09) for nivolumab plus ipilimumab versus -3·14 (-6·03 to -0·25) for sunitinib (p<0·0001), and for FACT-G total score being 4·77 (1·73 to 7·82) for nivolumab plus ipilimumab versus -4·32 (-8·54 to -0·11) for sunitinib (p=0·0005). Significant differences were also seen for four of five FKSI-19 domains (disease-related symptoms, physical disease-related symptoms, treatment side-effects, and functional wellbeing) and FACT-G physical and functional wellbeing domains. However, there was no significant difference between the treatment groups at week 103 in EQ-5D-3L visual analogue rating scale (VAS) scores, with mean change from baseline to week 103 of 10·07 (95% CI 4·35 to 15·80) for nivolumab plus ipilimumab and 6·40 (-1·36 to 14·16) for sunitinib (p=0·45). Compared with sunitinib, nivolumab plus ipilimumab reduced risk of deterioration in FKSI-19 total score (hazard ratio [HR] 0·54; 95% CI 0·46-0·63), FACT-G total score (0·63, 0·52-0·75), and EQ-5D-3L VAS score (HR 0·75, 95% CI 0·63-0·89) and UK utility scores (0·67, 0·57-0·80). INTERPRETATION: Nivolumab plus ipilimumab leads to fewer symptoms and better HRQoL than sunitinib in patients at intermediate or poor risk with advanced renal cell carcinoma. These results suggest that the superior efficacy of nivolumab plus ipilimumab over sunitinib comes with the additional benefit of improved HRQoL. FUNDING: Bristol-Myers Squibb and ONO Pharmaceutical.

The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies.

BACKGROUND: Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). METHODS: HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. RESULTS: In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. CONCLUSION: Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival.