Treating the untended: Real-world insights into enfortumab vedotin plus pembrolizumab for frail metastatic urothelial carcinoma patients excluded or underrepresented in clinical trials (GUARDIANS).

• DOI: 10.1200/jco.2025.43.16_suppl.e16548
• Publication Date: 2025-05-28T14:48:34Z
• Authors: Can Aydogdu; Stefanie Zschaebitz; Thomas Büttner; Marco Julius Schn...; Christopher Darr; Guenter Niegisch; Nina Holzwarth; Anna-Lisa Volk; Martin Hennig; Katrin Schlack; Subhajit Mandal; Julia Heinzelbecker; Frederik Wessels; Joschka Heil; Philipp Schmucker; Pia Paffenholz; Friedemann Zenger...; Eva Erne; Viktor Grünwald; Jozefina Casuscelli
• Keywords: Metastatic Urothelial Carcinoma; Urothelial cancer

e16548 Background: Patients with terminal renal failure (GFR <30 ml/min or dialysis), poor performance status (ECOG ≥2), and/or age ≥80 are often excluded underrepresented in pivotal clinical trials evaluating enfortumab vedotin and pembrolizumab (EV/P) as first-line (1L) treatment metastatic urothelial carcinoma (mUC). Consequently, data on safety efficacy these populations limited. This study evaluates EV/P outcomes this high-risk group. Methods: multicenter, real-world, retrospective included mUC patients receiving 1L who were (age ≥ 80) ineligible for the EV-302 trial due to GFR ml/min, ECOG ≥2. Endpoints overall progression free survival (OS, PFS), objective response rate (ORR), treatment-related adverse events (AE). Descriptive analyses evaluated frail patients. Results: A total of 116 from 18 German tertiary care centers treated between May 2022 December 2024. The median was 79 years (IQR 68–83), 20.7% having a 44.8% presenting ≥2, 49.1% aged ≥80. age-adjusted Charlson Comorbidity Index 6 4–8), highlighting high burden comorbidities population. ORR 54.1%, including an 8.1% complete rate. mPFS 7.5 months (95% CI 5.9–NR), mOS not reached. Any-grade AEs reported 72.2% patients, ≥grade 3 31.3%. most common peripheral neuropathy (33.0%) skin toxicity (23.3%). Among ≥80, 39% required dose reductions, compared 31% cohort, occurring after 68 days 42–137). Of all 18.1% discontinued progressive disease, only 31.3% them subsequent anti-cancer therapy. In contrary 26.7% permanently non-specified reasons, duration 89 40–180). Conclusions: real-world analysis suggests that demonstrates promising oncological efficacy, even highly those years. However, frequent discontinuations absence disease underscore need prospective studies evaluate more tolerable regimens interruptions strategies.