Single-center retrospective analysis of safety and efficacy of dose-reduced enfortumab vedotin (EV) in frail patients with metastatic urothelial carcinoma (mUC).

e16556 Background: EV is a Nectin-4 directed ADC with activity in mUC. EV monotherapy increased PFS and OS compared to salvage chemotherapy in pretreated mUC. EV + pembrolizumab increased PFS and OS compared to chemotherapy as first-line therapy and is being explored in the perioperative setting. Thus, EV will likely have an increasingly prominent role in the management of UC. However, EV is given until disease progression and has significant toxicities, especially for elderly or frail patients. Other than the initial dose escalation, no studies have reported the efficacy or safety of starting EV at a dose lower than the approved dose of 1.25 mg/kg. Methods: We performed a single-center retrospective analysis of patients treated with EV from 1/1/2020 to 12/25/2023. Data were collected by chart review including labs, imaging, and clinical documentation. Grades of toxicity were assigned based on CTCAE v5.0 criteria with available data. Radiographic response was determined by the investigator. We evaluated outcomes including ORR, PFS, OS, and EV-associated AEs, and compared these between patients who received 0.75 mg/kg (“low-dose”) and patients who received higher doses (“standard-dose”). Given the small sample size, we present only descriptive statistics. Results: We analyzed data from 18 patients treated with standard-dose EV and from 9 patients treated with low-dose EV. The low-dose group, compared with the standard-dose group, had a similar number of females (33% vs 44%) and non-whites (33% vs 28%), and higher median age at first EV dose (81 vs 68). The low-dose group had a lower rate of prior curative intent surgery (55% vs 78%) and upper tract disease (11% vs 50%), and fewer prior lines of treatment in the palliative setting (median 1 vs 2). In the low-dose group, ORR was 78% with CR in 33%. With a median follow up of 15.9 months, median PFS and median OS from EV initiation were not estimable. In the standard-dose group, ORR was 78% with CR in 28%. With a median follow up of 28.2 months, median PFS was 8.9 months and median OS was 24.1 months. The low-dose group had similar or lower grades of EV-associated AEs (Table). Conclusions: Patients treated with low-dose EV 0.75 mg/kg had similar responses compared to historical controls and a same-institution cohort of patients treated with standard-dose EV, with lower rates of GI toxicities, rash, and peripheral neuropathy. Findings are limited by small sample size, retrospective nature, and differences in baseline characteristics. Low-dose EV in elderly or frail patients with baseline comorbidities warrants prospective study. Table: see text