In a significant development for urothelial cancer treatment, researchers have discovered that certain adverse events associated with Enfortumab Vedotin (Padcev) therapy may actually indicate improved treatment outcomes. The findings, presented at the 2025 ASCO Genitourinary Cancers Symposium, suggest that patients who experience neuropathy, skin rash, or hyperglycemia during treatment demonstrate notably longer progression-free survival (PFS).
Key Clinical Findings
The study, conducted at Indiana University, analyzed data from 83 patients treated with at least two doses of Enfortumab Vedotin between 2018 and 2024. After a median follow-up of 14 months, researchers observed striking differences in progression-free survival based on the presence of specific adverse events.
Patients experiencing hyperglycemia showed the most substantial benefit, with a median PFS of 15.9 months. Those developing neuropathy and skin rash demonstrated median PFS of 10.6 and 8.6 months, respectively. In contrast, patients who did not experience any of these adverse events had a considerably shorter median PFS of 4.5 months.
Treatment Context and Patient Demographics
The study population included patients with locally advanced and metastatic bladder and upper tract urothelial carcinoma. Of the total cohort, 47 patients received Enfortumab Vedotin in combination with pembrolizumab (Keytruda), while 36 received it as monotherapy. The median age of participants was 69 years.
Disease distribution among patients showed varied metastatic sites, including lymph nodes (50%), lungs (41%), bones (35%), liver (19%), and brain (8%). The treatment was administered across multiple lines of therapy, with 52% receiving it as first-line treatment, 34% as second-line, 12% as third-line, and 2% as fourth-line therapy.
Recent Regulatory Development
These findings gain additional relevance in light of the FDA's December 15, 2023 approval of Enfortumab Vedotin in combination with pembrolizumab for locally advanced or metastatic urothelial cancer. This approval was supported by the phase 3 EV-302/KN-A39 trial, which demonstrated significant improvements in both overall survival and progression-free survival compared to platinum-based chemotherapy.
Clinical Implications
"Neuropathy, skin rash, and hyperglycemia are common adverse events associated with Padcev," noted Dr. Tareq K. Salous, the study's first author and assistant professor at Indiana University School of Medicine. These findings suggest that while these side effects require careful management, they may serve as potential biomarkers for treatment efficacy.
The observed correlation between specific adverse events and improved outcomes could have important implications for patient monitoring and treatment optimization. However, further research may be needed to understand the underlying mechanisms connecting these adverse events to improved survival outcomes.
