Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial.BACKGROUND
 The EV-201 trial (NCT03219333) demonstrated a clinically meaningful and durable response rate and a tolerable safety profile with enfortumab vedotin (EV) in patients with locally advanced/metastatic urothelial carcinoma (LA/mUC) treated with prior PD-1/PD-L1 inhibitor therapy and platinum-containing chemotherapy (cohort 1).  Patient-reported outcome (PRO) measures were included in EV-201 as exploratory endpoints.


 OBJECTIVE
 To evaluate PRO data for cohort 1 of EV-201 to better understand the relationship between EV therapy and health-related quality of life (HRQoL).


 DESIGN, SETTING, AND PARTICIPANTS
 Enrolled patients with LA/mUC who received EV were invited to electronically complete two HRQoL instruments (EORTC QLQ-C30 and EQ-5D-3L) at baseline and day 1 of each cycle until treatment discontinuation.


 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
 Patient demographics, completion and compliance rates, and PRO scores were analysed using descriptive statistics.  Selected EORTC QLQ-C30 scores were analysed post hoc using a repeated-measures mixed model.


 Among treated patients (n = 125), 95% completed both baseline questionnaires.  Compliance rates were ≥86% throughout the study.  Descriptive analyses showed that global health status, physical functioning, and symptom scores remained stable over time, with average scores similar at each cycle.  Lower pain and fatigue scores were observed in responders at cycles following an objective response.  Pain was lower at cycle 3 than at baseline in patients with bone metastases.  Mean EQ-5D-3L utility score (0.80 at baseline; range from 0.77 at cycle 2 to 0.91 at cycle 10) and visual analogue scale scores (66.9 at baseline; range from 65.5 at cycle 2 to 78.4 at cycle 10) remained similar over time.  Variability and the small sample size limited definitive conclusions.


 CONCLUSIONS
 PRO scores remained stable throughout EV treatment, further supporting the overall value of EV in the treatment of patients with LA/mUC.  The potential benefit of EV therapy on overall HRQoL and symptoms such as pain and fatigue is currently being explored.


 In this study of adult patients with advanced cancer of the urinary tract that progressed after previous medications, quality of life, ability to function, and symptoms did not worsen on treatment with enfortumab vedotin, which is an antibody + drug combination.  Some improvements in pain and fatigue were reported by patients, but further research needs to be conducted.  These data complement the efficacy and safety data from the EV-201 trial.
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