Certain AEs May Indicate Improved PFS With Enfortumab Vedotin for Urothelial Carcinoma
Improved progression-free survival in metastatic urothelial carcinoma was observed in patients experiencing neuropathy, skin rash, and hyperglycemia following enfortumab vedotin.
Some side effects of enfortumab vedotin may be linked to better outcomes in metastatic urothelial carcinoma.
Neuropathy, rash, and hyperglycemia after enfortumab vedotin (Padcev) treatment were linked to improved progression-free survival (PFS) in metastatic urothelial carcinoma, according to a poster presented at the 2025 ASCO Genitourinary Cancers Symposium.1
After a median follow-up of 14 months from the start of enfortumab vedotin treatment , neuropathy was reported in 30 patients (36%), skin rash in 32 patients (39%), and hyperglycemia in six patients (7%). The median PFS was 4.5 months in patients who did not experience neuropathy, skin rash or hyperglycemia; 10.6 months in those with neuropathy; 8.6 months in those with skin rash; and 15.9 months in those with hyperglycemia.
Between 2018 and 2024, a total of 83 patients were treated with at least 2 doses of enfortumab vedotin. Of these, 47 patients received the drug with pembrolizumab (Keytruda), while 36 received enfortumab vedotin as a single agent. The median age was 69 years. Metastatic sites included lymph nodes (50%), lungs (41%), bones (35%), liver (19%), and brain (8%). Enfortumab vedotin was used in the first-line setting in 43 (52%) patients, in the second-line setting in 28 (34%), in the third-line setting in 10 (12%), and in the fourth-line setting in 2 (2%).
Utilizing a query of the Indiana University bladder cancer database, investigators identified patients with locally advanced and metastatic bladder and upper tract urothelial carcinoma treated with enfortumab vedotin with or without pembrolizumab. Patients with variant histology were included. Toxicities were documented throughout treatment. The association of neuropathy, skin rash, and hyperglycemia with PFS was compared with that of patients without these adverse effects (AE) using the log-rank test.
“Neuropathy, skin rash, and hyperglycemia are common adverse events associated with Padcev, according to study authors,” first study author Tareq K. Salous, MD, and authors wrote in the abstract of the study.
Salous is an assistant professor of clinical medicine in the Department of Medicine, Division of Hematology/Oncology, at the Indiana University (IU) School of Medicine, IU Simon Comprehensive Cancer Center, and is an associate member of Experimental and Developmental Therapeutics, in Indianapolis.
More on the FDA Approval of This Combination
Prior to the presentation at the meeting, on December 15, 2023, the FDA approved enfortumab vedotin with pembrolizumab for locally advanced or metastatic urothelial cancer. The combination previously received accelerated approval for patients ineligible for cisplatin-based chemotherapy, according to the FDA’s website.
Approval was based on the phase 3 EV-302/KN-A39 trial (NCT04223856) an open-label, randomized study of 886 patients with locally advanced or metastatic urothelial cancer and no prior systemic therapy. Patients received either enfortumab vedotin plus pembrolizumab or platinum-based chemotherapy. The primary end points were overall survival (OS) and PFS.
Enfortumab vedotin plus pembrolizumab significantly improved OS (median 31.5 vs 16.1 months) and PFS (median 12.5 vs 6.3 months) compared with platinum-based chemotherapy.
Reference:
Salous T, Hassoun R, Althouse S, et al. Neuropathy, skin rash, and hyperglycemia as predictors of response to enfortumab vedotin in locally advanced and metastatic bladder and upper tract urothelial carcinoma. J Clin Oncol. 2025;43(suppl 5):771. doi:10.1200/JCO.2025.43.5_suppl.771.
