Dr. Rana McKay on the Enfortumab Vedotin Combo Receiving an FDA Nod for Advanced Urothelial Cancer

By Rana McKay, MD - Last Updated: April 10, 2023

Rana McKay, MD, Medical Oncologist and Associate Professor of Medicine, UC San Diego Health, shares how the FDA accelerated approval of enfortumab vedotin-ejfv with pembrolizumab impacts patients with locally advanced or metastatic urothelial carcinoma.

Dr. McKay: This data is super exciting. We saw the first splash of data from Cohort K at ESMO last year, which looked at the combination of pembrolizumab—which has known activity in urothelial cancer and is an FDA approved agent—and enfortumab vedotin – which is an antibody drug conjugate to Nectin-4. The data presented highlighted the activity of the combination in the frontline setting for patients with cisplatin-ineligible disease, demonstrating a confirmed objective response rate of over 64% in this population, which is really quite striking. There were toxicities, particularly skin reactions, peripheral neuropathy, and ocular disorders, but in general, they were lower grade and fairly well managed. Patients who have cisplatin-ineligible disease still constitute an unmet need. Thus, this is a huge advancement in the field and is certainly bringing up a lot of questions about what’s the best frontline strategy.

There’s currently a large phase 3 trial called EV-302, which looks at this combination in the frontline setting, but in both cisplatin-eligible and ineligible patients. Patients are randomized to receive enfortumab vedotin plus pembrolizumab versus cisplatin or carboplatin, depending on their ability to receive cisplatin plus gemcitabine. That trial is going to be critically important in shedding light on the role of this combination in a larger patient population.

One of the issues with this trial, EV-302, is it does not allow for maintenance avelumab based off of the JAVELIN Bladder 100 data. We have now seen that the new standard of care is platinum-based combination therapy with either cisplatin or carboplatin plus gemcitabine for patients who are chemotherapy-eligible, and then for those patients that don’t have primary progressive disease, putting them on maintenance avelumab. The EV-302 trial does not allow for maintenance avelumab, so there will continue to be that outstanding question of what to do in the maintenance setting.

Regardless, I think this is a huge win for the field and for patients. The data are quite exciting, and it is a pretty bold move to challenge this platinum in the frontline setting, because of its longstanding history and great efficacy. I believe this is going to change the way we approach patients with advanced urothelial carcinoma.