Enfortumab vedotin (EV) is an antibody-drug conjugate that specifically targets Nectin-4, a protein overexpressed in urothelial cancer cells. Both as a monotherapy and in combination with pembrolizumab, EV has shown improved overall survival (OS) compared to conventional chemotherapy in patients with locally advanced urothelial carcinoma, whether treated previously or not.

Eligible adult patients included those with locally advanced urothelial carcinoma. Patients in this case series were treated with a combination of enfortumab vedotin (1.25 mg/kg intravenously on days 1 and 8 of each 21-day cycle) and pembrolizumab (200 mg intravenously on day 1). The primary objectives of this case series were to assess overall response, pathological downstaging, and safety. Adverse events of interest were systematically documented and evaluated.

A total of 7 patients were included in this case series, with a median age of 68.9 years (range: 48 to 90 years), and 85.7% of patients were male. Five patients (71.4%) had cT3 disease, while two (28.6%) had cT4 disease. The disease originated in the upper urinary tract in 28.6% of patients, in the bladder in 57.1%, and in both the upper urinary tract and bladder in 14.3%. Most of the patients (85.7%) had pure urothelial carcinoma, while 14.3% had mixed histology. A complete response was seen in 42.9% (3 of 7) of patients, while partial responses were observed in 42.9% (3 of 7) of patients. The pathological downstaging rate was 85.7% (6 of 7), with the remaining patients not yet having undergone surgery. One patient received avelumab as subsequent therapy after partial cystectomy. Adverse events related to treatment were observed in 71.4% (5 of 7) of patients. The most frequent treatment-related events included pruritus (57.1%), followed by peripheral sensory neuropathy, hand-foot syndrome, hepatitis, and bullous dermatitis (all 14.3%). Importantly, there were no treatment-related adverse events of grade 3 or higher, and there were no instances of dose reductions or discontinuations due to treatment-related toxicities.

In summary, this case series highlights the potential of enfortumab vedotin in combination with pembrolizumab for treating advanced urothelial carcinoma. The treatment was associated with promising clinical efficacy, including pathological downstaging, and exhibited a manageable safety profile in this cohort of patients.