EV plus pembro approval reframes first conversation in MIBC diagnosis

The FDA's expanded approval of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for muscle-invasive bladder cancer—now covering cisplatin-eligible patients in the perioperative setting¹—fundamentally reframes the first clinical conversation urologists have with a newly diagnosed MIBC patient, according to María Natalia Gandur Quiroga, MD, MSc, of the Instituto de Oncología Ángel H. Roffo in Buenos Aires, Argentina.

"The major change is how we think about treatment planning before surgery," Gandur Quiroga said. For decades, neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy has been the standard for cisplatin-eligible patients. The KEYNOTE-B15/EV-304 trial (NCT04700124) challenged that standard directly, comparing perioperative EV plus pembrolizumab against neoadjuvant gemcitabine and cisplatin.

"This is not a metastatic-only strategy anymore," she said. "It brings an antibody-drug conjugate and immunotherapy into the curative-intent setting—before and after cystectomy."

The practical implication is a shift in the framing of the treatment decision. "Instead of asking only whether the patient should go directly to cystectomy or receive cisplatin-based chemotherapy first, we now need to discuss this perioperative systemic option more broadly," Gandur Quiroga said.

Medical oncology involvement, she emphasized, must come earlier than it historically has. The central question has changed: not "can this patient receive cisplatin?" but "what is the best systemic strategy to maximize cure before and after cystectomy?"

On the trial data, Gandur Quiroga interpreted the results as clinically meaningful rather than merely statistically positive—a distinction she considered important. Median event-free survival was not reached in the EV plus pembrolizumab arm vs 48.5 months with gemcitabine and cisplatin (HR 0.53), representing approximately a 47% relative reduction in the risk of an event. Overall survival also favored the experimental arm (HR 0.65).

"In the perioperative setting, overall survival is extremely important because we are treating with curative intent," she said. "Both event-free survival and overall survival moving in the right direction makes the result much more compelling."

She also underscored the strength of the comparator.

"This was not a weak control arm—it was gemcitabine and cisplatin as an actual standard neoadjuvant chemotherapy approach for cisplatin-eligible patients," Gandur Quiroga said. "That makes the results particularly relevant for daily practice."

She was equally direct about what remains unresolved: Follow-up continues to mature, subgroup analyses are needed to identify who benefits most, sequencing of later therapies after recurrence requires further study, and indirect comparison with other perioperative strategies—including NIAGARA (NCT03732677)—will be important context as the field integrates these data.

"This is more than a response rate story," she said. "It is a survival story in the curative-intent setting."

REFERENCE

1. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. US Food & Drug Administration. July 10, 2026. Accessed July 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-or-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-enfortumab-vedotin