Patient Preferences for First-Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: An Application of Multidimensional Thresholding.

Objectives: Patient preferences have the potential to influence the development of new treatments for locally advanced/metastatic urothelial carcinoma (la/mUC), and therefore we explored how patients with la/mUC value different attributes of first-line treatments.
Methods: An online preference survey and multidimensional thresholding (MDT) exercise were developed following a targeted literature review and qualitative interviews with physicians, patients with la/mUC, and their caregivers. Treatment attributes included two benefits (overall response rate [ORR], pain related to bladder cancer [scored 0-100; 100 being the worst pain possible]) and four treatment-related risks (peripheral neuropathy, severe side effects, mild to moderate nausea, mild to moderate skin reactions). A Dirichlet regression was used to estimate average preference weights. Marginal utility and the reduction in ORR that patients would accept in exchange for a 10-point decrease or a 10% decrease in other attributes were calculated.
Results: A total of 100 patients were recruited and self-completed the survey and MDT. Mean patient age was 64.9 years (standard deviation, 7.6), 54% were female, and 38% identified as white. All included treatment attributes had a statistically significant impact on preferences. Changes in ORR had the largest impact, followed by cancer-related pain and treatment-related risks. Patients were willing to accept an 8.4% decrease in ORR to reduce their pain level by 10 points or a 7.8% decrease in ORR to reduce the risk of peripheral neuropathy by 10%. For a 10% decrease in severe side effects, mild to moderate nausea, or skin reaction, patients would accept decreases in ORR of 5.5%, 3.7%, or 3.4%, respectively.
Conclusions: Of the attributes tested, changes in ORR were most important to patients. Patients made tradeoffs between treatment attributes indicating that a lower ORR may be acceptable for an improvement in other attributes such as reduced cancer-related pain or the risk of treatment-related adverse events.
Competing Interests: Declarations. Funding: This study was funded by Seagen Inc, which was acquired by Pfizer in December 2023, and by Astellas Pharma Inc. Conflicts of Interest: Mallory Farrar and Zsolt Hepp are former employees of, and held stock in Seagen Inc, which was acquired by Pfizer in December 2023. Lisa Mucha is an employee of Astellas Pharma Inc. Christine Michaels-Igbokwe, Sebastian Heidenreich, Katelyn Cutts, Nicholas Krucien, and Natasha Ramachandran are employees of Evidera, which received funding from Seagen Inc. and Astellas Inc. in connection with this study. Sebastian Heidenreich is an editorial board member of The Patient, and was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Sebastian Heidenreich is also a minority stockholder of Thermo Fisher Scientific as part of his employment with Evidera. John L. Gore and David J. Benjamin have previously received consulting fees from Seagen Inc. Andrea B. Apolo and Nicholas I. Simon have no conflicts of interest to disclose. Authors of this manuscript include former employees of Seagen Inc, which was acquired by Pfizer in December 2023, and Astellas Pharma Inc. Availability of Data and Material: The data supporting the findings of this study are available within the article and its supplementary materials. Ethics Approval: The study protocol was approved by the Salus institutional review board (study number: 22147-01B). The study investigators were not employed by the study sponsors (Seagen Inc, which was acquired by Pfizer in December 2023, and Astellas Pharma Inc.), and any patient data were deidentified prior to being provided to study sponsors. Consent to Participate: Patients indicated their interest in participating and gave informed consent. Consent for Publication: Not applicable Code Availability: All software applications used are commercially available. Author Contributions: Concept and design: Andrea B. Apolo, Christine Michaels-Igbokwe, Nicholas I. Simon, David J. Benjamin, Mallory Farrar, Zsolt Hepp, Lisa Mucha, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran, and John L. Gore; acquisition of data: Christine Michaels-Igbokwe, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, and Natasha Ramachandran; analysis and interpretation of data: Andrea B. Apolo, Christine Michaels-Igbokwe, Nicholas I. Simon, David J. Benjamin, Mallory Farrar, Zsolt Hepp, Lisa Mucha, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran, and John L. Gore; drafting of the manuscript: Andrea B. Apolo, Christine Michaels-Igbokwe, Nicholas I. Simon, David J. Benjamin, Mallory Farrar, Zsolt Hepp, Lisa Mucha, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran, and John L. Gore; critical revision of the paper for important intellectual content: Andrea B. Apolo, Christine Michaels-Igbokwe, Nicholas I. Simon, David J. Benjamin, Mallory Farrar, Zsolt Hepp, Lisa Mucha, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran, and John L. Gore; obtaining funding: Mallory Farrar, Zsolt Hepp, and Lisa Mucha; administrative, technical, or logistic support: Christine Michaels-Igbokwe, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran; and supervision: Andrea B. Apolo, Christine Michaels-Igbokwe, Nicholas I. Simon, David J. Benjamin, Mallory Farrar, Zsolt Hepp, Lisa Mucha, Sebastian Heidenreich, Katelyn Cutts, Nicolas Krucien, Natasha Ramachandran, and John L. Gore. All authors were involved in the design and conduct of the study, analysis and interpretation of the data, and preparation and review of the manuscript. All authors read and approved the final version of the manuscript.
(© 2024. The Author(s).)