Treatment with the antibody-drug conjugate enfortumab vedotin-ejfv has been found to significantly increase survival of patients with metastatic urothelial carcinoma, according to results from the phase III EV-301 clinical trial. These findings were presented by Thomas Powles, MD, PhD, and colleagues at the 2021 Genitourinary Cancers Symposium (Abstract 393); they were also simultaneously published in The New England Journal of Medicine.

Thomas Powles, MD, PhD

One of the most widely used treatments for this type of cancer is chemotherapy, which works by targeting all the cells in the body, successfully acting upon cancer cells, but also affecting noncancer cells, causing side effects. A novel class of drugs, the antibody-drug conjugates, have an antibody attached to a chemotherapy-like drug. The antibody specifically targets and attaches to cancer cells, bringing with it the chemotherapy-like drug, which then act only on the cancer cells and ignore normal cells in the body.

EV-301

The trial involved 608 patients in 19 countries. It tested the efficacy of enfortumab vedotin in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.

Patients were randomly assigned 1:1 to receive either enfortumab vedotin (at a dose of 1.25 mg/kg body weight on days 1, 8, and 15 of a 28-day cycle) or investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle. The trial's primary endpoint was overall survival.

Results

The risk of death was 30% lower with enfortumab vedotin than with chemotherapy. Median overall survival was 12.88 months in patients treated with the antibody-drug conjugate vs 8.97 months in patients treated with chemotherapy (hazard ratio [HR] = 0.70, 95% confidence interval [CI] = 0.56–0.89, P = .001).

Median progression-free survival was 5.6 months with enfortumab vedotin vs 3.7 months with chemotherapy (HR = 0.62, 95% CI = 0.51–0.75, P < .001). The overall response rate was 40.6% in the enfortumab vedotin arm vs 17.9% in the chemotherapy arm.

Rates of treatment-related adverse events, including serious events, were similar between the two arms (93.9% in the enfortumab vedotin arm and 91.8% in the chemotherapy arm). Rates of grade ≥ 3 adverse events were approximately 50% in both groups; decreased neutrophil count (13.4%) and white blood cell count (6.9%) were more common in patients treated with chemotherapy, and maculopapular rash (7.4%) was more common in those treated with enfortumab vedotin.

Dr. Powles, Professor of Genitourinary Oncology at Queen Mary University of London, and Director of Barts Cancer Centre, Barts Health NHS Trust, said, "This new type of drug has led to a survival advantage in bladder cancer, which has been difficult to achieve in this disease. It reduced the death rate by 30% and beat chemotherapy in every setting, so this really is a big deal."

Disclosure: For full disclosures of the study authors, visit coi.asco.org or nejm.org.