Perioperative Enfortumab Vedotin-Pembrolizumab in MIBC

Neoadjuvant cisplatin-based chemotherapy remains the standard treatment for muscle-invasive bladder cancer. However, recent clinical trial results demonstrate that perioperative enfortumab vedotin pembrolizumab significantly improves patient outcomes compared to standard chemotherapy.

Efficacy of Enfortumab Vedotin Pembrolizumab in MIBC

The phase 3 KEYNOTE-B15 trial evaluated adults with muscle-invasive bladder cancer eligible for cisplatin-based therapy and radical cystectomy. Specifically, investigators randomly assigned 405 participants to receive perioperative enfortumab vedotin plus pembrolizumab. Furthermore, 403 participants received standard neoadjuvant cisplatin plus gemcitabine followed by surgery.

At two years, the immunotherapy combination achieved superior outcomes. Consequently, estimated event-free survival reached 79.4% in the combination group compared to 66.2% in the chemotherapy arm. Moreover, overall survival showed a significant benefit, reducing the hazard for death by 35%. Additionally, pathological complete response occurred in 55.8% of patients receiving the combination compared to 32.5% in the chemotherapy group.

Safety and Clinical Implications for Oncologists

High surgical completion rates occurred in both trial groups. Specifically, 86.7% of participants in the combination group and 89.6% in the control group underwent radical cystectomy. Therefore, neoadjuvant treatment did not compromise surgical feasibility.

However, safety monitoring revealed distinct toxicity profiles. Grade 3 or higher treatment-related adverse events occurred in 71.3% of combination patients versus 45.9% of chemotherapy patients. Thus, clinicians must carefully manage adverse events when administering this novel perioperative regimen.

Frequently Asked Questions

Q1: What is the primary advantage of perioperative enfortumab vedotin plus pembrolizumab?

The combination significantly improves event-free survival, overall survival, and pathological complete response rates compared to standard neoadjuvant cisplatin-gemcitabine chemotherapy.

Q2: Did neoadjuvant immunotherapy delay or reduce cystectomy completion rates?

Overall, surgical completion rates remained high, with 86.7% of combination participants and 89.6% of chemotherapy participants undergoing cystectomy.

Q3: How does the safety profile compare between the two treatment arms?

In contrast, grade 3 or higher adverse events occurred more frequently with the combination regimen (71.3%) than with standard chemotherapy (45.9%).

References

1. Galsky MD et al. Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer. N Engl J Med. 2026 Jul 23. doi: 10.1056/NEJMoa2601486. PMID: 42485627.
2. Vulsteke C et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026;394(13):1257-1269.