Trailblazing Urothelial Cancer Treatments (Podcast)

For more than four decades, patients with urothelial cancer have been treated with cisplatin. However, more than 50% of those patients are ineligible for the chemotherapy drug due to comorbidities. Now there are promising new therapies effective in both cisplatin-eligible and cisplatin-ineligible patients – enfortumab vedotin (EV) and pembrolizumab.

In a phase 3 trial of platinum-eligible patients, the response rate of patients with advanced urothelial cancer who were given a combination of EV and pembrolizumab was 68% compared to 44% who received chemotherapy. In addition, their overall survival rate doubled.

“It’s really unprecedented data that we have seen so far,” says Shilpa Gupta, MD, director ofGenitourinary Medical Oncology at Cleveland Clinic’s Taussig Cancer Institute. “It’s become the undisputed frontline standard.”

In a recent episode of Cleveland Clinic’s Cancer Advances podcast, Dr. Gupta provides an overview of the clinical trial. She discusses:

• How cisplatin eligibility or ineligibility impacts cancer treatment
• Results of a phase 1/2 clinical trial of EV and pembrolizumab on cisplatin-ineligible patients
• Phase 3 trial methods and results
• Toxicities with the EV-pembrolizumab combination, including peripheral neuropathy and rash
• Potential for the therapy combination in a neoadjuvant setting
• What’s on the horizon in bladder cancer research

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Cancer Advances episodes at clevelandclinic.org/podcasts/cancer-advances or wherever you get your podcasts.

Excerpt from the podcast:

Podcast host Dale Shepard, MD, PhD: This [phase 3 trial] was for patients with metastatic disease. What's going on with these combinations in a neoadjuvant setting?

Dr. Gupta, MD: That's also a great question. There's already phase 3 trials being done in both cisplatin-eligible and cisplatin-ineligible muscle invasive cancer with EV-pembro. So, in cisplatin-ineligible, it is compared to single agent pembro or upfront cystectomy. And in the cisplatin-eligible, it's compared to GemCis [gemcitabine-cisplatin]. So, we are waiting for the studies to accrue and see.

And that will again, I think, change the landscape if it moves to that setting. So, it's really an exciting time. This combination is something that people are really excited about in every setting.

Dr. Shepard: Historically, neoadjuvant studies in bladder have been tough. Has the excitement of this combination in the metastatic setting sort of eliminated some of that difficulty doing a neoadjuvant study?

Dr. Gupta:I would say we don't know yet. But we are taking part in those studies, and I think that it is somewhat more toxic than we see in the metastatic setting, especially after surgery. It becomes a little bit of a challenge to continue EV-pembro for a long time. And that's why I'm really looking forward to the data from these neoadjuvant studies as to what was the tolerability. Because in my experience, it has been more difficult than in the metastatic setting.