Patient And Caregiver Benefit-Risk Preferences For Treatment In Advanced Urothelial Carcinoma

448 Background: Checkpoint blockade therapy has demonstrated improved survival in second-line urothelial carcinoma and is also active as first-line (1L) therapy in locally advanced / metastatic urothelial carcinoma (mUC) patients (PTs) who are cisplatin-ineligible / PD-L1 high or platinum-ineligible regardless of PD-L1 level. This study quantified trade-offs between efficacy and adverse events (AEs) associated with 1L treatments for mUC that PTs and caregivers (CGs) are willing to make. Methods: PTs with mUC and CGs were recruited via advocacy groups to complete a cross-sectional online survey assessing treatment preferences with a discrete choice experiment (DCE) employing descriptive language. In a series of tasks, PTs and CGs chose their preferred option from two alternative treatment profiles varying on six select attributes: overall survival (OS), progression-free survival (PFS), and AEs including: all grades (AG) neuropathy; and G3/4 nausea/vomiting, fatigue, and diarrhea. Hierarchical Bayesian modelling estimated preference weights for each attribute level. Results: PTs (N=152) had a mean age of 60 years; 68% had Stage 4 UC. CGs (N=151) had a mean age of 53 years and cared for PTs with a mean age of 62; most CGs (67%) cared for a PT with Stage 4 UC. While attributes had the same rank order of importance for both PTs and CGs, improving OS from 10 to 22 months was 31% more important than improving PFS from 2 to 10 months for PTs, whereas OS and PFS were more similarly valued by CGs. CGs placed less importance than PTs on OS relative to the importance of G3/4 nausea/vomiting, G3/4 diarrhea, and AG neuropathy (all P<0.01). Despite these differences, OS was at least twice as important than reduction in AEs for both cohorts. To accept increases in G3/4 nausea/vomiting by 21%, G3/4 fatigue by 23%, G3/4 diarrhea by 7%, and AG neuropathy by 5%, OS would need to improve by 2.2, 2.3, 1.2, and 0.5 months (PTs) and 6.6, 5.5, 3.0, and 1.1 months (CGs), respectively. Conclusions: Trade-offs made between efficacy and specific AEs for mUC are nuanced between PTs and CGs, with CGs desiring larger OS benefits to accept higher AE risk. These findings suggest a need for deeper discussions between PTs, CGs and physicians about treatment decisions.