Daniel Petrylak: Hi, I'm Dr. Daniel Petrylak, Professor of Medicine and Urology at the Smilow Cancer Center, Yale University. I'm in Las Vegas at the AUA Meeting, talking about some of the most exciting abstracts. It's my pleasure today to have Dr. Taka Nakamura from Japan, who's going to be talking about the EV-301 trial and those patients who were not eligible to go on study. How were these patients different than those patients from the EV-301 trial?

Kazutaka Nakamura: Yeah, the EV-301 trial excluded patients with poor performance status, low hemoglobin, and impaired renal function. Yet in their clinical practice, many patients receiving enfortumab vedotin treatment actually fall into these categories. So we asked a simple and important question. Is EV still safe and effective in patients who were ineligible for the trial?

Daniel Petrylak: And what were your findings?

Kazutaka Nakamura: We retrospectively analyzed 55 patients with EV, and 43% of patients were trial ineligible. So there is no significant difference between the patients who are ineligible and eligible. And also overall survival was not a significant difference between the group.

Daniel Petrylak: So these patients had the same proportion of liver metastases as well as lymph node metastases, the same visceral disease as you would expect from the EV-301 trial?

Kazutaka Nakamura: Almost is the same.

Daniel Petrylak: That's important because we know that EV works extremely well in patients with liver mets, as well as in the other sites of disease. So you're showing a very similar survival and progression-free survival with these patients. What about toxicity? Was the toxicity any different?

Kazutaka Nakamura: Yeah, adverse events are almost the same between ineligible and eligible patients.

Daniel Petrylak: Interesting. So the neuropathy was the same. The rates of skin rash were the same. Those are the most, to me, the important side effects that need to be monitored with this drug.

Kazutaka Nakamura: It's a way to manage the adverse events for ineligible people. Nonresponders were more common in the eligible group, and 8 out of 13 patients received over 10 cycles. Still, early discontinuation due to AEs didn't differ significantly. Regarding ineligible patients, yeah, those who experienced adverse events had to stop the therapies.

Daniel Petrylak: But I think this has got actually important implications for practice even though this is a small trial. And it's not a prospective study. It sounds like it's more of a retrospective trial than prospective. But certainly in the United States, for those patients who are considered to be platinum-ineligible or cisplatin-ineligible, we use EV pembro in those individuals.

There are some who feel that if the patient has a poor performance status, that they just want to go with the pembro and not with the EV. I think this gives us more confidence that you potentially can add the EV in the situation, because you're probably not adding much more in terms of toxicity. So if a patient is platinum-ineligible, it's not inappropriate to think about using the combination therapy for these patients.

Kazutaka Nakamura: In our study, the patients with performance status score over 2, yeah, is a negative factor for PFS. Yeah, clearly. Yeah. But kidney dysfunction is not a clear factor for negative PFS.

So EV doesn't rely on clearance in the same way, so like cisplatin or carboplatin. So in our study, patients with creatinine clearance under [INAUDIBLE] had a similar PFS and OS to those above that threshold. Yeah, this supports EV as a viable treatment in the renal-impaired patient.

Daniel Petrylak: That's really an important point because as we know a lot of these patients do have renal dysfunction because of obstruction, because of damage that may have been done from other treatments previously, particularly platinum compounds or cisplatin. So it does simply again give us some guidance as to how we can treat our patients in this situation. So I think to summarize some of your data, let me see if I have this right.

Kazutaka Nakamura: All right.

Daniel Petrylak: You took a cohort of patients who were not eligible to go on EV-301. And EV-301 is a randomized trial that compared enfortumab in patients who had one prior chemotherapy and immune checkpoint therapy to standard-of-care chemotherapy, which could have been vinflunine or docetaxel. And what you're showing is that those patients also were able to safely receive, who were not eligible, to safely receive enfortumab.

And as I mentioned before, this has important practice implications for our patients because now with the EV pembro data and using this upfront, a patient who may not be eligible to receive cisplatin chemotherapy or platinum-based chemotherapy in the past and you were reluctant to give them any other treatment, you may have just given them a checkpoint. Now, I think there's further justification for doing both drugs at the same time.

Kazutaka Nakamura: Right.

Daniel Petrylak: Terrific. Do you have any other final comments?

Kazutaka Nakamura: EV-301 is a third-line treatment for metastatic urothelial carcinoma. So it's just a final therapy for the patients. So we have to initiate the therapy for all patients. So even if they have poor performance status, low hemoglobin, or low creatinine, yeah, EV is—all patients had a good response to EV. So EV is a good therapy as a final therapy.

But EV-302 is a first-line treatment, yeah. Yeah, I think its key point is toxicity. Yeah.

Daniel Petrylak: Exactly.

Kazutaka Nakamura: Yeah, there are tips to chemotherapy. So we experienced interstitial pneumonia grade 3/3 for cases.

Daniel Petrylak: Well, this just shows you also the importance of monitoring the immune system. And back in the EV-301 trial, there was data that was reported about interstitial pneumonitis as well. So it does occur with both drugs.

Kazutaka Nakamura: Yeah.

Daniel Petrylak: So great. Thank you so much for your abstract. We enjoyed it and are looking forward to future presentations from you.

Kazutaka Nakamura: Thank you for inviting me.