FDA Expands Pembrolizumab Label for Muscle-Invasive Bladder Cancer

The Food and Drug Administration (FDA) has expanded the approval of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with enfortumab vedotin-ejfv (Padcev) for the treatment of muscle-invasive bladder cancer (MIBC).

This landmark decision allows the regimen to be used as neoadjuvant treatment prior to surgery, followed by adjuvant treatment after cystectomy for all adults with MIBC who are candidates for surgery. This update significantly broadens the therapeutic landscape, as the regimen was previously limited in this setting to patients who were cisplatin-ineligible.

The KEYNOTE-B15/EV-304 trial

The approval was based on data from the KEYNOTE-B15/EV-304 trial, an open-label, multicenter, randomized phase 3 study. The trial enrolled 808 patients with previously untreated MIBC who were eligible for cisplatin-based chemotherapy and candidates for radical cystectomy with pelvic lymph node dissection. Participants were randomized 1:1 to receive either the perioperative combination of pembrolizumab and enfortumab vedotin-ejfv or the standard-of-care neoadjuvant gemcitabine and cisplatin followed by surgery.

The primary efficacy measure for the trial was event-free survival (EFS), with overall survival (OS) serving as a secondary endpoint. Results demonstrated that the combination therapy provided statistically significant improvements in both EFS and OS compared to the chemotherapy arm. Specifically, the median EFS was not reached for the pembrolizumab/enfortumab vedotin arm, while the gemcitabine/cisplatin arm saw a median EFS of 48.5 months (hazard ratio [HR] 0.53; p-value <0.0001). Similarly, the median OS was not reached in either study arm, but the combination showed a clear survival advantage (HR 0.65; p-value 0.0029).

Nursing implications: Safety and vigilance

For oncology nurses, understanding the safety profile of this combination is vital for patient monitoring and education. The FDA noted that the overall safety profile in this trial was consistent with previous studies of the combination in urothelial cancer. However, both agents carry significant warnings that require proactive management.

Pembrolizumab is associated with immune-mediated adverse reactions, which can affect any organ system, as well as infusion-related reactions. Nurses should also be aware of risks regarding embryo-fetal toxicity and complications in patients undergoing allogeneic hematopoietic stem cell transplantation.

Enfortumab vedotin-ejfv carries specific warnings for severe skin reactions, hyperglycemia, and peripheral neuropathy. Additionally, clinicians should monitor for pneumonitis, ocular disorders, and infusion site extravasation. Educating patients on the early signs of these reactions is a critical component of nursing care to ensure timely intervention.

Dosing and administration schedules

The administration of this perioperative regimen involves a multi-phase approach that requires careful coordination. For cisplatin-eligible patients, the recommended neoadjuvant pembrolizumab dose is either 200 mg every three weeks or 400 mg every six weeks. This is given alongside enfortumab vedotin-ejfv at 1.25 mg/kg (capped at 125 mg for patients over 100 kg) on Days 1 and 8 of a 21-day cycle. This neoadjuvant phase consists of four cycles over 12 weeks.

Following surgery, the adjuvant phase begins. Enfortumab vedotin-ejfv is continued for five additional cycles every three weeks. Pembrolizumab is continued as well, either at 200 mg every three weeks for 13 cycles or 400 mg every six weeks for seven cycles. The combined duration of both drugs in the adjuvant setting is 15 weeks, while the total duration of adjuvant therapy (including pembrolizumab monotherapy) extends to 39 weeks. Nurses should ensure that when both drugs are administered on the same day, pembrolizumab is given after enfortumab vedotin-ejfv.

Regulatory context

This review was facilitated by Project Orbis, an initiative that allows for the concurrent submission and review of oncology products among international partners, including regulatory agencies in Australia, Canada, Switzerland, the United Kingdom, and Israel. The FDA utilized the Assessment Aid and granted the application priority review, ultimately approving the treatment five weeks ahead of the goal date.

Healthcare providers are encouraged to report any suspected serious adverse events to the FDA’s MedWatch Reporting System. This expanded approval represents a significant shift in the standard of care for MIBC, offering a potent perioperative option for a broader patient population.

Reference

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