Drs. Gupta, Koshkin on EV-103 Cohort K Results and Toxicities

By Shilpa Gupta, MD, Vadim Koshkin, MD - August 4, 2023

Shilpa Gupta, MD, Cleveland Clinic, and Vadim Koshkin, MD, University of California, San Francisco, continue their discussion on the EV-103 trial with reference to outcomes and toxicities associated with enfortumab vedotin plus pembrolizumab in cohort K.

Dr. Koshkin: I’d like to touch on cohort K, which was different but similar in population and treatment. Can you comment on how it contributes to the data you presented?

Dr. Gupta: Certainly. Cohort K was a randomized cohort aiming to assess the additional benefit of the combination compared to EV monotherapy. The results were consistent with cohort A, showing higher response rates with EV/pembro and a similar toxicity profile. It served as reassurance and evidence for registration purposes to demonstrate the combination’s benefits.

Dr. Koshkin: You raised an important point about the indefinite treatment duration in EV-103, which is influenced by toxicities. Could you elaborate on the toxicity profile of the combination and any signals observed after 4 years of follow-up?

Dr. Gupta: The key toxicities observed with the combination were rash, peripheral neuropathy, and hyperglycemia. There was an increased incidence of bullous dermatitis-like rashes, which requires close monitoring as it can be severe. Peripheral neuropathy is often underplayed by patients, so providers need to be vigilant and manage it appropriately. The combination can also lead to diabetes and diabetic ketoacidosis in patients without a pre-existing condition.

Regarding treatment duration, we don’t believe all patients need lifelong EV treatment. Intensification early on followed by pembro maintenance is something we may explore in the future. In my practice, I am quick to adjust doses and hold treatments to maintain patient benefit.

Dr. Koshkin: This combination has received accelerated approval in the United States. Has it changed your practice, and how do you select between EV/pembrolizumab and carboplatin plus avelumab for cisplatin-ineligible front-line patients?

Dr. Gupta: It is an additional option, but as of now, my practice is not entirely changed, primarily based on the level one evidence from JAVELIN Bladder 100 trial. We also have the main cab trial, adding cabozantinib to avelumab, which we offer to patients. For some select patients with specific comorbidities, such as poorly controlled diabetes or baseline neuropathy, I may choose carboplatin plus avelumab instead of EV/pembro. Also, in patients with bulky liver metastases requiring a rapid response, the combination may be preferable due to its activity in liver lesions. Ultimately, I follow the level 1 evidence and use EV/pembro as a discussion point for patients who prefer not to receive chemotherapy followed by avelumab.

Dr. Koshkin: It is great to have this as an additional option. But yes, I think we are still waiting on the randomized data from EV-302 to confirm a lot of this practice.

View their previous discussion on EV-103 Design and Long-Term Cohort A Results.