TY - JOUR
T1 - 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
T2 - Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial
AU - McGregor, Bradley
AU - O'Donnell, Peter H.
AU - Balar, Arjun
AU - Petrylak, Daniel
AU - Rosenberg, Jonathan
AU - Yu, Evan Y.
AU - Quinn, David I.
AU - Heath, Elisabeth I.
AU - Campbell, Mary
AU - Hepp, Zsolt
AU - McKay, Caroline
AU - Steinberg, Joyce
AU - Regnault, Antoine
AU - Mazerolle, Flora
AU - Galsky, Matthew D.
N1 - Funding Information:
Financial disclosures: Matthew D. Galsky certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Bradley McGregor has served as an advisory board member and consultant for Astellas, AstraZeneca, Bayer, Exelixis, Genentech, Janssen, Nextar, Pfizer, Eisai, Dendreon, BMS, Calithera, and Seagen; and has received research funding from BMS, Calithera Biosciences, Exelixis, and Seagen. Peter H. O’Donnell has acted as a consultant and advisory board member for Merck; has equity ownership in AbbVie (formerly Allergan); has received honoraria from Astellas, AstraZeneca, Atheneum Partners, Dedham Group, FirstWord Publication, Genentech, Harrison Consulting Group, Health Advances, Inovio, Janssen, Kantar Health, Merck, OncLive, Parexel, Pfizer, Quintiles, Schlesinger Associates, and Seagen; has received research funding from Acerta, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Genentech, Janssen, Merck, and Seagen; and has other relationships with Janssen, Dragonfly, and Nektar. Arjun Balar has served as an advisory board member and consultant for Astellas, AstraZeneca, Cerulean Pharma, Genentech, Incyte, Merck, Pfizer, EMD-Serono, Bristol-Myers Squibb, GSK, and Seagen; has received honoraria from AstraZeneca, Genentech, and Merck; and has received research funding from AstraZeneca, Genentech, Merck, and Seagen. Daniel Petrylak has served as an advisory board member and consultant for Astellas, AstraZeneca, Bayer, Bellicum Pharma, Dendreon, Exelixis, Ferring, Johnson & Johnson, Lilly, Millennium, Medivation, Pfizer, Roche, Sanofi, and Tyme; has equity ownership in Bellicum Pharma and Tyme; has received research funding from Agensys, Astellas, Medivation, AstraZeneca, Bayer, Clovis onc, Dendreon, Endocyte, Genentech, Innocrin Pharma, Johnson & Johnson, Lilly, MedImmune, Millennium, Merck, Novartis, Pfizer, Progenics, Roche, Sanofi, Seagen, and Sotio; and has provided expert testimony for Celgene and Sanofi. Jonathan Rosenberg has served as an advisory board member and consultant for Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, EMD Serono, Genentech/Roche, Gilead/Immunomedics, GSK, Janssen, Lilly, Merck, Mirati, Pfizer, Pharmacyclics, QED Therapeutics, Tyra Biosciences, and Seagen; has received honoraria from Medscape, Peerview, RTP, and UpToDate; has received research funding from Agensys, AstraZeneca, Bayer, Genentech, Incyte, Mirati Therapeutics, QED, and Seagen; and has received travel expenses from BMS and Genentech. Evan Y. Yu has served as a consultant or advisor for Janssen, Bayer, Merck, Dendreon, Seagen, Clovis, Advanced Accelerator Applications, Exelixis, AbbVie, and Sanofi; and has received institutional research from Daiichi Sankyo, Dendreon, Taiho, Pharmacyclics, Blue Earth, Bayer, Merck, and Seagen. David Quinn is an employee of the University of Southern California; has received institutional research funding from Seagen, MSD, and Novartis; has served as an advisor/board member for Astellas, AstraZeneca, Bayer, BMS, Dendreon, Exelixis, Roche, Janssen, MSD, Novartis, Pfizer, and Sanofi; and has received travel and accommodation expenses from Pfizer, MSD, AstraZeneca, BMS, and Roche. Elisabeth I. Heath has served as a consultant or advisor for Agensys; has received honoraria from Bayer AG, Dendreon, Sanofi, and Seagen; has served on a speaker bureau for Sanofi; has received institutional research funding from Tokai Pharmaceuticals, Seagen, Agensys, Dendreon, Genentech, Roche, Millennium, Celldex, Inovio Pharmaceuticals, Celgene, Zenith Epigenetics, Merck, AstraZeneca, Esanik, Oncolys BioPharma, Curemeta, BMS, eFFECTOR Therapeutics, Fortis, Astellas Pharma, Medivation, AstraZeneca, Ignyta, Synta, Caris Life Sciences, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, Plexxikon, Corcept Therapeutics, and Infinity Pharmaceuticals; and reports other relationships with Caris Centers of Excellence. Mary Campbell is an employee of Seagen and owns stock in the company. Zsolt Hepp is an employee of Seagen and owns stock in the company. Caroline McKay is an employee of Astellas Pharma and owns stock in the company. Joyce Steinberg is an employee of Astellas Pharma and owns stock in the company. Antoine Regnault is an employee of Modus Outcomes, which received consulting fees from Seagen in connection with this study. Flora Mazerolle is an employee of Modus Outcomes, which received consulting fees from Seagen in connection with this study. Matthew Galsky has served as an advisory board member and consultant for Aileron Therapeutics, Astellas, AstraZeneca, BioMotiv, BMS, Dendreon, Dracen, EMD Serono, Genentech, GSK, Incyte, Inovio Pharma, Janssen, Lilly, Merck, Novartis, NuMab, Pfizer, and Seagen; has equity ownership in Rappta Therapeutics; holds patents/royalties for Methods and compositions for treating cancer and related methods (20120322792); and has received research funding from AstraZeneca, BMS, Dendreon, Genentech, Janssen, Merck, and Novartis.
Funding Information:
Funding/Support and role of the sponsor: The study was sponsored by Seagen Inc. and Astellas Pharma Inc. The sponsors played a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. This work was supported in part by National Cancer Institute Cancer Center Support grant P30 CA008748.
Publisher Copyright:
© 2022 European Association of Urology
PY - 2022/5
Y1 - 2022/5
N2 - 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. Results and limitations: 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. Patient summary: 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.
AB - 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. Results and limitations: 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. Patient summary: 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.
KW - Enfortumab vedotin
KW - Health-related quality of life
KW - Patient-reported outcomes
KW - Urothelial cancer
UR - http://www.scopus.com/inward/record.url?scp=85124530140&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2022.01.032
DO - 10.1016/j.eururo.2022.01.032
M3 - Article
C2 - 35168844
AN - SCOPUS:85124530140
SN - 0302-2838
VL - 81
SP - 515
EP - 522
JO - European Urology
JF - European Urology
IS - 5
ER -