Work

Real-World Enfortumab Vedotin ± Pembrolizumab Treatment-Based Toxicities and Associations With Survival in Advanced Urothelial Carcinoma

Year: 2025

Type: article

Abstract: Structured Abstract Introduction Enfortumab vedotin (EV) in combination with pembrolizumab (P) is the first-line treatment for advanced urothelial carcinoma, but real-world toxicity profiles and associations with survival remain an area of active investigation. Patients and Methods Here, we first perform a single-center (University of Pennsylvania) retrospective study of EV ± P patients to characterize frequency and clinical importance of five relevant toxicities (skin reaction, neuropathy, ocular disorder, hyperglycemia, and pneumonitis). We associate these toxicities with survival and then evaluate these findings in a larger national cohort (Flatiron Health Research Database [FHRD]). Results We find that toxicities were common in the single-center cohort, with skin reaction (60%) and neuropathy (47%) most frequent, but toxicity-related discontinuation or hospitalization were less frequent (13%). Without a landmark analysis, multiple toxicities were linked to survival, but landmark analysis to address immortal time bias preserved only the skin reaction-survival association (Penn: HR=0.28, 95% CI: 0.14-0.58; FHRD: HR=0.69, 95% CI: 0.53-0.90). Conclusions These findings highlight the clinical relevance of EV ± P related toxicities, demonstrate the importance of accounting for immortal time bias in associations of these toxicities with survival, and add to a growing evidence base showing a survival association with skin toxicity in EV ± P treated patients. Future prospective studies are needed to evaluate skin toxicity as a favorable marker for survival. MicroAbstract Enfortumab vedotin (EV) in combination with pembrolizumab (P) is the first-line treatment for advanced urothelial carcinoma, but real-world toxicity profiles and associations with survival remain an area of active investigation. In this retrospective study using both single-center (n=123) and national cohort (n=1631) data, we find that skin toxicity, but not other toxicities, in EV ± P patients is associated with improved survival (single center: HR=0.28, 95% CI: 0.14-0.58; national cohort: HR=0.69, 95% CI: 0.53-0.90) after accounting for immortal time bias with a landmark analysis.

Source: Clinical Genitourinary Cancer

DOI: 10.1016/j.clgc.2025.102474

Authors: Martin Kurian, Ronac Mamtani, Omar Elghawy, Vivek Nimgaonkar

Institutions: Hospital of the University of Pennsylvania, University of Pennsylvania, Johns Hopkins University, Johns Hopkins Hospital

Language: English

Topic: Bladder and Urothelial Cancer Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,530