Video

Dr. Grivas on Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma

Petros Grivas, MD, PhD, discusses the investigation of enfortumab vedotin and pembrolizumab in metastatic urothelial carcinoma.

Petros Grivas, MD, PhD, physician, Fred Hutchinson Cancer Center, associate professor, Division of Medical Oncology, University of Washington (UW) School of Medicine, clinical director, Genitourinary Cancers Program, UW Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the investigation of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in metastatic urothelial carcinoma.

Historically, achieving cures for patients with metastatic urothelial carcinoma has been a challenge, specifically among patients who are platinum refractory, since they have a poor prognosis, Grivas says. Novel agents, such as the antibody-drug conjugate enfortumab vedotin, have demonstrated activity as a single agent in metastatic urothelial carcinoma; however, in later settings, response rates tend to fall.

Investigators hope to continue to expand the treatment armamentarium for metastatic urothelial carcinoma with the addition of subsequent therapies. As these therapies emerge, learning how to sequence them and use them in potential combinations could produce more benefit, Grivas says. 

One example of a novel combination is enfortumab vedotin and pembrolizumab. The phase 1/2 EV-103 trial (NCT03288545) examined this combination and enfortumab vedotin alone in patients with locally advanced or metastatic urothelial cancer, eliciting efficacy and tolerability, Grivas explains. Data from cohort K of the trial presented at the 2022 ESMO Congress showed that among 76 patients treated with the combination, the overall response rate (ORR) was 64.5% with a median duration of response (DOR) that was not reached. In 73 patients treated with enfortumab vedotin alone, the ORR was 45.2% with a median DOR of 13.2 months.

In December 2022, the FDA granted a priority review to a supplemental biologics license applications for enfortumab vedotin and pembrolizumab used in combination for the treatment of patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy. The combination is under further evaluation in the ongoing phase 3 KEYNOTE-A39/EV-302 trial (NCT04223856) in patients with previously untreated advanced urothelial carcinoma.

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