4 minutes reading time (721 words)

Enfortumab Vedotin for Advanced Urothelial Carcinoma With Peter H. O'Donnell, MD

Peter H. O'Donnell, MD.

The FDA recently approved enfortumab vedotin (Padcev®, Astellas Pharma US, Inc.) for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after treatment with platinum-based chemotherapy and anti–programmed cell death protein 1 (anti–PD-1) or anti–programmed death ligand 1 (anti–PD-L1) therapy. The approval was based on EV-201, a phase 2 trial in which enfortumab vedotin produced a high rate of response in patients with locally advanced or metastatic urothelial carcinoma. In this interview with i3 Health, Peter H. O'Donnell, MD, Associate Professor of Medicine at the University of Chicago and one of EV-201's investigators, discusses the benefits of enfortumab vedotin for patients with urothelial carcinoma and shares his advice for oncologists as they begin prescribing this medication to their patients.

Can you comment on the significance of the approval of enfortumab vedotin for patients with locally advanced or metastatic urothelial carcinoma previously treated with anti–PD-1/PD-L1 therapy and platinum-based chemotherapy?

Peter H. O'Donnell, MD: The approval of enfortumab vedotin has huge significance. This drug has very impressive activity in a refractory population. The activity that it has in patients with liver metastases is especially notable, because those are the patients that traditionally have the worst prognosis and for whom few therapies would typically work. Having a new option that can provide disease control for such patients addresses a major unmet need.

How does enfortumab vedotin compare with other treatments for patients with locally advanced or metastatic urothelial carcinoma?

Dr. O'Donnell: Enfortumab vedotin has a unique mechanism of action that really sets it apart. I think of it as a sort of hybrid between chemotherapy and immunotherapy, which are the types of treatment to which these patients are typically exposed. Chemotherapy has been the backbone and the standard of care for many decades, and immunotherapy has come into the scene in the past several years. Enfortumab vedotin is a hybrid of these two types of treatment, in that it has an antibody portion but also a cytotoxic portion. From the standpoint of the patient experience, it is also somewhat "in the middle" of what they are used to in terms of tolerability. It's not as easy as immunotherapy is for many patients, but it's also not as difficult as chemotherapy is for many patients.

How do you see the treatment of advanced urothelial carcinoma evolving, both in light of this approval and in the future?

Dr. O'Donnell: I think we are potentially going to see other antibody-drug conjugates coming down the pipeline, and that could be very interesting. I also think that we're going to see the use of enfortumab vedotin explored in other earlier disease settings, rather than just in the refractory population. Because it has such impressive activity, one wonders if it could move earlier in the disease course.

Do you have any words of advice for community oncologists and urologists as they begin treating patients with locally advanced or metastatic urothelial carcinoma with enfortumab vedotin?

Dr. O'Donnell: The drug does need to be given on a routine weekly dosing schedule (three weeks out of every four). When patients have prolonged holds of the drug for toxicity or other reasons, their disease will often start to grow again due to the drug's relatively short half-life. In patients who are developing toxicity, earlier dose reductions seem to be a way for patients to tolerate the drug better and subsequently stay on it for longer.

About Dr. O'Donnell

Peter H. O'Donnell, MD, is an Associate Professor of Medicine in the Section of Hematology/Oncology at the University of Chicago. He is also a member of the University of Chicago's Committee on Clinical Pharmacology and Pharmacogenics. Dr. O'Donnell specializes in the treatment of bladder cancer and other genitourinary malignancies. He has led numerous clinical trials investigating novel treatments for patients with these diseases, and much of his research focuses on the association between individual patients' genetic profiles and their therapeutic outcomes.

For More Information

Rosenberg JE, O'Donnell PH, Balar AV, et al (2019). Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol, 37(29);2592-2600. DOI:10.1200/JCO.19.01140

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health. 

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