Assessment of eligibility criteria in advanced urothelial cancer (aUC) trials based on ASCO-FCR recommendations.

453 Background: American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) underscored the need to broaden eligibility criteria in cancer trials to increase patient accrual, expand access to investigational treatments, and enhance generalizability of study results (Kim et al., Clin Cancer Res 2021). While eligibility criteria intend to prioritize patient safety and define a specific study population, these criteria are often based on outdated standards and may not be reflective of real-world practice. Our study aimed to characterize the proportion of aUC trial eligibility criteria according to the ASCO-FCR statement. Methods: Protocols indexed on ClinicalTrials.gov with start dates from June 30, 2012 to June 30, 2022 were evaluated. MeSH terms used in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (bladder cancer OR upper tract urothelial carcinoma OR upper tract urothelial cancer)”. International studies enrolling patients aged 18 and over in phases I-III were included. Studies examining multiple cancer types as well as those involving localized treatments (e.g., surgery or ablation), radiation therapy, and prognostic tools were excluded. Analyses of eligibility criteria focused on those highlighted in the ASCO-FCR statement; descriptive statistics were used to define the frequency of eligibility criteria and chi-square and Fisher’s exact test were used to determine their association with treatment type. Results: Overall, 205 urothelial cancer trials were assessed, with 37 (18.0%) having publicly accessible data. Of these, 13 (35.1%) evaluated combination therapy, 11 (29.7%) evaluated immunotherapy, 8 (21.6%) evaluated targeted therapy, and 5 (13.5%) evaluated chemotherapy. HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies were found to be exclusion criteria in 89.2% (33/37), 56.8% (21/37), 35.1% (13/37), and 5.4% (2/37) of studies, respectively. While brain metastases, concurrent malignancies, and HBV/HCV positivity were found to be independent of the class of therapy, a statistically significant association was observed with HIV positivity. Specifically, trials evaluating combination therapy (100.0%), immunotherapy (100.0%) and targeted therapy (87.5%) more frequently included HIV positivity as an exclusion criterion as compared to chemotherapy trials (40.0%). Conclusions: A modest percentage of a UC studies from the last decade were observed to report overly restrictive eligibility criteria as defined by the ASCO-FCR statement. HIV positivity and HBV/HCV positivity were commonly identified exclusion criteria, despite limited evidence that these criteria significantly impact drug efficacy and tolerability. Reassessing and updating eligibility criteria will ensure that the resulting data is more reflective and inclusive of a real-world population.