Enfortumab vedotin (EV) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs standard-of-care chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (UC), according to primary results of the EV-301 study presented at the 2021 Genitourinary Cancers Symposium.

“EV is the first therapy to show a significant survival advantage over standard chemotherapy in patients with treatment-experienced locally advanced/metastatic UC,” said Thomas Powles, MBBS, MRCP, MD, who presented the findings.

EV is an antibody-drug conjugate (ADC) that targets Nectin-4, which is highly expressed by UC cells. EV was previously found to demonstrate promising activity in a single-arm study; the phase 3 EV-301 study (NCT03474107) was initiated to confirm EV’s superiority to chemotherapy in this pretreated patient population.

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Investigators of the open-label trial randomly assigned 608 patients with locally advanced or metastatic UC to receive either EV or chemotherapy. To be eligible to enroll, patients must have received a prior platinum-containing chemotherapy regimen and experienced radiographic progression or relapse during or after checkpoint inhibitor therapy. The primary end point was OS; secondary end points included PFS, objective response rate (ORR), disease control rate (DCR), and safety.

Data from the prespecified interim analysis demonstrated a significant improvement in OS with EV. At the data cutoff (July 15, 2020), the median OS was 12.8 months with the ADC vs 8.9 months with chemotherapy (HR, 0.70; 95% CI, 0.56-0.89; P =.001).

EV was also found to prolong PFS. The median PFS was 5.5 months with EV compared with 3.7 months with chemotherapy (HR, 0.62; 95% CI, 0.51-0.75; P <.00001). The ORR (40.6% vs 17.9%) and DCR also favored EV (71.9% vs 53.4%; %; P <.001 for both).

The rates of any-grade treatment-related adverse events (TRAEs) were similar between groups. Serious TRAEs of any grade were seen in 23% of patients in each arm.

The rates of grade 3 or higher TRAEs were also comparable between the 2 treatment groups, affecting 51% and 50% of patients in the EV and chemotherapy arms, respectively.

Rash maculopapular (7%), fatigue (6%), and decreased neutrophil count (6%) were the 3 most common grade 3 or higher TRAEs among those who received EV. Decreased neutrophil count (13%), anemia (8%), and a decrease in white blood cell count (7%) were the most prevalent grade 3 or greater TRAEs in the chemotherapy group.

Powles et al concluded that, “with robust clinical benefit and a tolerability safety profile, EV is a new standard of care for this aggressive disease.”

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Astellas Pharma, Inc.


Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 393.