Dr Vulsteke on the FDA Approval of Enfortumab Vedotin Plus Pembrolizumab for Cisplatin-Ineligible MIBC

“All [eligible] patients should receive enfortumab vedotin plus pembrolizumab when it’s available in the region they live in. I can only hope it will be widely available around the world soon.”

Christof Vulsteke, MD, PhD, head of the Integrated Cancer Center Ghent, discussed the clinical significance of the FDA approval of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC), contextualizing the decision within longstanding gaps in care for this population.

The approval was based on findings from the phase 3 KEYNOTE-905 study (NCT03924895), which evaluated enfortumab vedotin/pembrolizumab in patients with MIBC who were ineligible for cisplatin-based chemotherapy. The antibody-drug conjugate enfortumab vedotin targets Nectin-4, which is highly expressed in urothelial carcinoma, whereas pembrolizumab provides immune checkpoint inhibition through PD-1 blockade. Together, the combination leverages complementary mechanisms of action that have already demonstrated activity in advanced and metastatic bladder cancer, now extended into earlier-stage disease.

From a clinical perspective, Vulsteke noted that the FDA approval directly addresses an unmet need for cisplatin-ineligible patients, who historically have had no clearly defined standard-of-care systemic therapy in the neoadjuvant setting. He underscored that, based on the available data, eligible patients should receive enfortumab vedotin plus pembrolizumab when access permits, as the regimen offers the potential to improve pathologic and survival outcomes in a group previously underserved by existing treatment paradigms.

Vulsteke also highlighted the broader implications of the KEYNOTE-905 results, noting emerging signals suggesting benefit beyond the cisplatin-ineligible population. Whereas the trial was primarily designed for cisplatin-ineligible patients, preliminary reports have indicated potential improvements in progression-free survival and overall survival in cisplatin-eligible cohorts as well. He emphasized that full dataset maturation will be critical to understanding how broadly this regimen may be applied across the MIBC spectrum.

Finally, Vulsteke stressed the importance of global access and regulatory alignment. Although this FDA approval represents a critical milestone, he expressed hope that similar approvals will follow in Europe and other regions, enabling oncologists worldwide to incorporate this combination into routine practice.