ASCO GU 2021: Enfortumab Vedotin in Previously Treated Urothelial Cancer - Results of EV-301 & EV-201 Cohort 2 Discussion

( In this presentation, Arlene O. Siefker-Radtke, MD from the University of Texas MD Anderson Cancer Center provided a discussion on two presentations on Enfortumab Vedotin (EV)  in previously treated urothelial cancer. She first reviewed the results of EV-301 (Abstract 393) which provided level 1 evidence of overall survival benefit with EV compared to single-agent chemotherapy in patients who progressed on platinum chemotherapy and immune checkpoint blockade. The trial schema and relevant overall survival data are re-shown below. EV also demonstrated a progression-free survival benefit and improved overall response rates to 41% from 18% with single-agent chemotherapy.



This clinical benefit does come at some toxicity, specifically higher incidence of maculopapular rash, however, EV is associated with lower rates of febrile neutropenia and overall cytopenias compared to chemotherapy. Treatment withdrawal rates were similar across groups. EV is now approved by the FDA for third-line treatment of advanced urothelial carcinoma.


Dr. Seifker-Radtke then summarized the findings of EV-201 cohort 2, presented in (Abstract 394). This was a non-comparative phase 2 trial of EV in platinum-naïve/cisplatin ineligible/anti-PD-1 axis progressive patients with overall response rate as the primary endpoint. The blinded independent review overall response rate was 52%, and the overall median survival was reasonably good for this disease state at 14.7 months. With regards to side effects as compared to the platinum-eligible cohort, there were numerically higher rates of skin reactions, neuropathy and hyperglycemia.

The reasons for the higher toxicity in EV-201 (the cisplatin-ineligible cohort) are not entirely clear. The presenter hypothesized that the higher rates of hyperglycemia in obese patients may reflect underlying fatty liver, which could have increased the toxicity of the drug. Indeed, the label for EV notes that concentrations of the active metabolite MMAE increase in mild hepatic impairment.

She concluded by congratulating the two study teams. Studies of EV earlier in the disease course of advanced urothelial carcinoma and in combination with pembrolizumab will continue to define the role of this drug in urothelial cancers.

Presented by: Arlene O. Siefker-Radtke, MD, The University of Texas MD Anderson Cancer Center

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021