Enfortumab Vedotin Shows Efficacy in Advanced Urothelial Carcinoma Outside Clinical Trials
Key Insights
Enfortumab vedotin (EV) combined with pembrolizumab demonstrates a high disease control rate in advanced urothelial carcinoma (search) (aUC) patients outside clinical trials.
Alterations in KMT2D (search) and TP53 (search) genes are associated with shorter progression-free survival (PFS) and overall survival (OS) in patients treated with EV/P.
Baseline neuropathy does not lead to inferior outcomes with EV treatment, suggesting comorbidities should not preclude its use with careful monitoring.
Enfortumab vedotin (EV), both as a monotherapy and in combination with pembrolizumab (EV/P), continues to demonstrate efficacy in treating advanced urothelial carcinoma (search) (aUC) patients in real-world settings, according to data presented at the European Society for Medical Oncology (ESMO) Congress 2024. The UNITE study, a multisite retrospective analysis, assessed the outcomes of EV-based treatments in patients with aUC, including those with comorbidities often excluded from clinical trials, such as neuropathy and diabetes.
Enfortumab Vedotin Plus Pembrolizumab Outcomes
One analysis from the UNITE study (Abstract 1988P) evaluated the efficacy of EV/P outside of clinical trials and explored potential biomarkers associated with treatment benefit. The study included 118 patients with available next-generation sequencing data. The results indicated a disease control rate (DCR) of 84% (95% CI, 77%-90%) and an objective response rate (ORR) of 51% (95% CI, 42%-60%). Researchers found that alterations in the KMT2D (search) (HR, 2.2; 95% CI, 1.0-4.5) and TP53 (search) (HR, 2.3; 95% CI, 1.2-4.2) genes were associated with shorter progression-free survival (PFS), while alterations in TP53 (HR, 2.3; 95% CI, 1.0-5.4) were linked to shorter overall survival (OS).
These findings suggest that while EV/P maintains a high DCR in real-world settings, the ORR may be more modest compared to first-line clinical trials. The identification of TP53 (search) and KMT2D (search) alterations as potential predictors of inferior outcomes could help refine treatment strategies.
Efficacy in Patients with Neuropathy and Diabetes
A separate analysis (Abstract 1989P) focused on the efficacy of EV in aUC patients with baseline neuropathy and/or diabetes mellitus, conditions that often lead to exclusion from clinical trials. The study included 666 patients, with subgroups having neuropathy (193), diabetes (77), both (46), or neither (343). The analysis revealed that baseline neuropathy was associated with significantly lower PFS (HR, 0.81; 95% CI, 0.66-0.98), but no significant difference in OS (HR, 0.86; 95% CI, 0.69-1.08). Baseline diabetes was not associated with significant differences in either PFS (HR, 1.19; 95% CI, 0.93-1.53) or OS (HR, 1.20; 95% CI, 0.91-1.59).
The researchers concluded that the presence of baseline neuropathy or diabetes should not preclude the use of EV in treating aUC. However, they emphasized the importance of careful monitoring for toxicities related to neuropathy, diabetes, and EV itself when using the treatment in these patient populations. This study reinforces the applicability of EV in a broader patient population, including those with common comorbidities.