Cutaneous adverse events (cAEs) caused by enfortumab vedotin are associated with improved survival in patients with locally advanced or metastatic urothelial cancer, according to research published in JAMA Dermatology.
The link between enfortumab vedotin-induced cutaneous toxicity and improved survival remained after accounting for immortal time bias and exposure to immune checkpoint inhibitors (ICIs), study researchers reported.
In this retrospective study, the researchers evaluated cAEs, progression-free survival (PFS), and overall survival (OS) in 449 patients with locally advanced or metastatic urothelial cancer who received enfortumab vedotin between 2020 and 2025 at Mass General Brigham and the Dana-Farber Cancer Institute.
A total of 172 patients were treated with enfortumab vedotin only, and the remaining patients in the analysis were treated with enfortumab vedotin plus either pembrolizumab (n=256) or a non-ICI agent (n=21).
Overall, 206 patients experienced cAEs, among which pruritis (n=85) was the most common. Grade 3 or higher cAEs occurred in 39 patients. Among all cutaneous adverse events observed in the study, 127 patient-cases were attributed to enfortumab vedotin.
The median time from the first enfortumab vedotin infusion to the onset of the worst cAEs was 17 days, with 62.6% of patients experiencing their worst cutaneous toxicity within 30 days.
In a multivariable Cox proportional hazards regression model that accounted for immortal time bias, researchers found that experiencing enfortumab vedotin-induced cAEs was independently linked to improved PFS compared with no enfortumab vedotin-induced toxicity (hazard ratio [HR], 0.60; 95% CI, 0.43-0.82; P <.001).
Similarly, enfortumab vedotin-induced cAEs were independently associated with improved OS (HR, 0.46; 95% CI, 0.31-0.67; P <.001).
“The protective association of [enfortumab vedotin]-induced cAEs remained consistent across multiple landmark points,” the researchers noted.
Cutaneous adverse events not attributed to enfortumab vedotin were not significantly linked with either PFS or OS, the researchers found. However, non-enfortumab vedotin-induced cAEs were protective for OS among patients who were treated with both enfortumab vedotin and ICIs (HR, 0.55; 95% CI, 0.33-0.92; P =.02).
When the researchers stratified enfortumab vedotin-induced cAEs by early (15 days or less) or late onset, only the early-onset events had a protective effect for PFS and OS.
Severe enfortumab vedotin-induced cAEs were not linked to significantly worse OS or PFS at any time, the researchers found.
The findings suggest that cAEs could serve as an “early biomarker of therapeutic effectiveness” in patients treated with enfortumab vedotin, the researchers wrote.
“Further prospective studies of standardized dermatologic assessment and molecular characterization are needed to better understand the causes, mitigation strategies, and survival associations of [enfortumab vedotin]-induced cAEs,” the researchers concluded.
Disclosures: There was no funding listed for this study. Some study authors disclosed conflicts of interest. Please see the original reference for complete disclosures.
