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Enfortumab Vedotin-ejfv: Antibody-Drug Conjugate for Advanced Urothelial Carcinoma

By: Celeste L. Dixon
Posted: Thursday, March 18, 2021

In an open-label, phase III randomized trial involving more than 600 patients in 19 countries with locally advanced or metastatic urothelial carcinoma, enfortumab vedotin-ejfv significantly prolonged median overall survival, compared with standard chemotherapy. All of these patients had previously received platinum-based chemotherapy treatment and a PD-1 or PD-L1 inhibitor. The results of EV-301 were published in The New England Journal of Medicine.

Enfortumab vedotin, explained Daniel P. Petrylak, MD, of Yale School of Medicine in New Haven, Connecticut, and colleagues, is an antibody-drug conjugate directed against Nectin-4. This cell-adhesion molecule is highly expressed in urothelial carcinoma and may contribute to tumor-cell growth and proliferation. The compound links “a fully human monoclonal antibody specific for Nectin-4 [with] monomethyl auristatin E, an agent that disrupts microtubule formation.” In this aggressive disease, they wrote, “targeted delivery of monomethyl auristatin E results in cell-cycle arrest and apoptosis.”

Half the patients received enfortumab vedotin at a dose of 1.25 mg/kg of body weight on days 1, 8, and 15 of a 28-day cycle. The other half received investigator-selected chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle.

The antibody-drug conjugate treatment significantly prolonged the median overall survival—the primary endpoint—compared with standard chemotherapy (12.88 vs. 8.97 months; P = .001). The median progression-free survival was also longer with enfortumab vedotin versus chemotherapy (5.55 vs. 3.71 months; P < .001). Treatment-related adverse events and events of grade 3 or higher frequently occurred in both arms (93.9% and 51.4% with enfortumab vedotin and 91.8% and 49.8% with chemotherapy, respectively).

“Because of the superior overall survival benefit observed at the planned interim analysis, the trial was stopped early,” explained Dr. Petrylak and co-investigators. “Future analyses of [its] quality-of-life data will further contextualize the efficacy and safety results.”

Disclosure: The study authors’ disclosure information can be found at nejm.org.



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