Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy

Abstract

Background and objective: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL).

Methods: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration.

Key findings and limitations: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy.

Conclusions and clinical implications: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301.

Patient summary: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.

Keywords: Antineoplastic agents; Cancer pain; Immunoconjugates; Patient-reported outcome measures; Urinary bladder neoplasms.

Fig. 1 –

Quality of Life Questionnaire Core 30 scores at week 12 by treatment group. (A) Global health status/quality of life and functioning scales. (B) Symptom scales. For functioning scales, negative numbers indicate that chemotherapy is better than EV. For symptom scales, negative numbers indicate EV is better than chemotherapy. Chemo = chemotherapy; CI = confidence interval; EV = enfortumab vedotin; LS = least squares; SE = standard error; W12 = week 12.

Fig. 2 –

Adjusted least-squares mean change in Quality of Life Questionnaire Core 30 global health status score from baseline with 95% confidence interval by treatment group. EV = enfortumab vedotin; LS = least squares. ^aAn additional post hoc analysis (F test) revealed that the variance in estimates of the adjusted change from baseline across the first 12 wk of treatment between the two arms was significantly different (p = 0.02), supporting considerable variability for the chemotherapy arm.

Fig. 3 –

Confirmed improvements in scores for Quality of Life Questionnaire Core 30 scales. CI = confidence interval; EV = enfortumab vedotin; OR = odds ratio. Only patients with baseline values allowing for an improvement in score for the respective scale were included in the responder analysis. ^aOR > 1.00 favors EV versus chemotherapy.

Fig. 4 –

Time to first confirmed clinically meaningful improvement. (A) Estimate of global health status/quality of life. (B) Results for Quality of Life Questionnaire Core 30 scales based on primary thresholds. Scores for financial difficulties were not included, as estimates were large because of the small number of events. Chemo = chemotherapy; CI = confidence interval; EV = enfortumab vedotin; HR = hazard ratio; NYR = not yet reached.

Fig. 5 –

Time to first confirmed clinically meaningful deterioration. (A) Estimate of global health status/quality of life. (B) Results for Quality of Life Questionnaire Core 30 scales based on primary thresholds. Chemo = chemotherapy; CI = confidence interval; EV = enfortumab vedotin; HR = hazard ratio; NYR = not yet reached.