Interim data from a clinical trial investigating the efficacy of enfortumab vedotin (EV) on bladder cancer are promising. In cisplatin-ineligible patients with local advanced or metastatic urothelial cancer who had received prior therapy with an immune checkpoint inhibitor, 52% of participants achieved a confirmed objective response rate (ORR) after receiving EV therapy [1]. The EV-201 trial (NCT03219333) –started in October 2017 and slated for completion in May 2025– is investigating the efficacy and safety of EV administered to patients with locally advanced or metastatic urothelial cancer who have previously been treated with PD-1/PD-L1 inhibitors. The study has 2 cohorts: patients who have undergone platinum-based chemotherapy, and patients who are cisplatin-ineligible/platinum-naïve. Dr Balar (NYU Langone Medical Oncology, New York City, USA) shared results from the second cohort at ASCO GU 2021. The cisplatin-ineligible cohort consisted of 89 participants who received 1.25 mg/kg EV intravenously on days 1, 8, and 15 of each 28-day cycle for a median treatment duration of 6 months. The primary endpoint of ORR, utilizing Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and confirmed by an independent review facility, was achieved by 52% of the participants. Additionally, 20% of participants achieved a complete response. Median duration of response was 10.9 months, median progression-free survival was 5.8 months, and median overall survival was 14.7 months. The safety profile matched the pre-existing safety profile of EV. Four deaths were deemed treatment-related; all occurred in patients aged >75 with multiple co-morbidities. Causes of death were acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome, and pneumonitis. Adverse events included alopecia (51%), peripheral neuropathy (47%), fatigue (34%), rash (61% all grade), and hyperglycemia (10% all grade). Researchers are optimistic that the favorable ORR and safety profile of EV make it a reasonable therapeutic option in the management of patients with locally advanced or metastatic urothelial cancer who have failed previous lines of therapy.

  1. Balar A. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with local advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. EASCO Genitourinary Cancers Symposium, 11-13 February 2021.