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Expert Point of View: Arlene O. Siefker-Radtke, MD


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“Now we know enfortumab vedotin-ejfv is here to stay in the armamentarium of treatment for advanced urothelial cancer,” said Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, during her discussion of both EV-301 and EV-201.

“As we saw, overall survival was quite good in EV-301, with a 12.8-month median survival compared with 8.9 months with single-agent chemotherapy. The clinical activity comes at the risk of toxicity. The drug appears to be safe and tolerable in this patient cohort. The rates of adverse events and grade 3 adverse events were similar to those of single-agent chemotherapy. Enfortumab vedotin is now approved by the U.S. Food and Drug Administration as third-line treatment of metastatic urothelial cancer,” she told listeners at the virtual meeting.

Turning to EV-201, Dr. Siefker-Radtke said the survival was “quite good” in platinum-ineligible patients treated with prior immunotherapy. “We had the sense that the rates of some of the adverse events were slightly higher [in EV-201] than in EV-301. Many of the deaths occurred in the first 30 days in patients with an elevated body mass index [BMI],” she noted. Those with preexisting hyperglycemia and an elevated BMI had higher rates of grades 3 and 4 hyperglycemia.

“We can manage the toxicity with enfortumab vedotin,” Dr. Siefker-Radtke continued. “Dose reductions are not needed for renal impairment, and it does seem that mild hepatic impairment led to a 40% increase in monomethyl auristatin E, and morbidity was increased in patients with liver dysfunction. Use of enfortumab vedotin should be avoided in patients with moderate-to-severe hepatic impairment.”

“I do think liver dysfunction plays a role in the development of toxicity with this tumor. In patients with an elevated BMI, a fatty liver could interfere with clearance by the liver. “Follow the recommendations to hold the drug for glucose > 250 mg/dL. This could be the sign that you hit the upper limit of the drug,” she advised.

Dr. Siefker-Radtke noted the impressive activity of the drug in patients with visceral and liver metastases in EV-301 and, in particular, in those with bone metastases. “This appears to be very helpful in controlling bone pain in many patients,” she said.

“Although this drug is currently approved in the third-line setting, we eagerly await the studies of enfortumab vedotin and pembrolizumab in the front-line setting,” she concluded. 

Publisher's Note: This article was originally published in the March 25, 2021 issue of The ASCO Post.

DISCLOSURE: Dr. Siefker-Radtke has served as a consultant or advisor to AstraZeneca, Basilea, Bavarian Nordic, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, Merck, Mirati Therapeutics, the National Comprehensive Cancer Network, Nektar, and Seattle Genetics; has received research funding from Basilea, BioClin Therapeutics, Bristol Myers Squibb, Janssen, MSD, Michael and Sherry Sutton Fund for Urothelial Cancer, Nektar, the National Institutes of Health, and Takeda; and holds intellectual property in “methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.”


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Enfortumab vedotin-ejfv continues to move the needle forward as a validated treatment option for advanced urothelial carcinoma. At the 2021 Genitourinary Cancers Symposium, results from the phase III EV-301 study1 and EV-201 Cohort 22 provided support for the use of this agent in both patients...

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