The treatment landscape for muscle-invasive bladder cancer (MIBC) continues to shift rapidly toward perioperative systemic strategies that aim not only to improve pathological response, but also to reduce recurrence risk and extend survival.
On April 20, 2026, Merck announced that the U.S. Food and Drug Administration granted priority review to supplemental Biologics License Applications for KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Padcev (enfortumab vedotin-ejfv), for cisplatin-eligible patients with MIBC. The FDA assigned a PDUFA date of August 17, 2026.
If approved, these regimens would extend the pembrolizumab–enfortumab vedotin perioperative strategy into the cisplatin-eligible population and could establish the first perioperative option spanning patients with MIBC regardless of cisplatin eligibility.
What the FDA Review Is Based On
The regulatory applications are supported by the phase 3 KEYNOTE-B15/EV-304 trial, which compared perioperative pembrolizumab plus enfortumab vedotin followed by surgery against standard neoadjuvant gemcitabine plus cisplatin followed by surgery in cisplatin-eligible patients with MIBC.
According to Merck’s announced results, the regimen demonstrated a statistically significant and clinically meaningful improvement in event-free survival and overall survival, along with improvement in pathologic complete response. Merck has reported that the regimen reduced the risk of event-free survival events by 47% and the risk of death by 35%versus standard neoadjuvant chemotherapy and surgery.
This is especially notable because cisplatin-based neoadjuvant chemotherapy has long remained the standard perioperative approach for eligible patients, despite persistent recurrence rates after cystectomy. Merck states that nearly half of patients treated with standard therapy still experience recurrence.
Enfortumab Vedotin and Pembrolizumab vs Chemotherapy in Advanced Urothelial Carcinoma
Why This Matters in Clinical Practice
This update matters because it signals a possible change in how clinicians think about perioperative treatment in MIBC.
Historically, cisplatin eligibility has defined treatment pathways. Patients able to receive cisplatin were directed toward neoadjuvant chemotherapy, while cisplatin-ineligible patients had fewer evidence-based perioperative options. That divide has already started to narrow with the U.S. approval of pembrolizumab plus enfortumab vedotin for cisplatin-ineligibleMIBC based on KEYNOTE-905. The new priority review now pushes that strategy into the cisplatin-eligible setting as well.
If approved, this would mean that an immunotherapy-plus-ADC perioperative regimen could potentially become a treatment option across a much broader MIBC population, rather than being restricted by platinum fitness alone.
KEYNOTE-B15 at a Glance
KEYNOTE-B15 enrolled 808 patients with cisplatin-eligible MIBC. Patients were randomized to receive either perioperative pembrolizumab plus enfortumab vedotin with radical cystectomy and pelvic lymph node dissection, or standard neoadjuvant gemcitabine/cisplatin followed by surgery. The primary endpoint was event-free survival, and key secondary endpoints included overall survival and pathologic complete response rate.
The trial adds to a growing body of phase 3 evidence supporting the pembrolizumab–enfortumab vedotin combination across bladder cancer settings. Merck notes that the combination has now shown an overall survival benefit in three phase 3 bladder cancer trials: KEYNOTE-B15 in cisplatin-eligible MIBC, KEYNOTE-905 in cisplatin-ineligible or cisplatin-declining MIBC, and KEYNOTE-A39 in locally advanced or metastatic urothelial carcinoma
Safety and Treatment Context
The press release announcing the review focuses on regulatory progress and topline efficacy rather than a full surgical or adverse-event dataset for KEYNOTE-B15. However, Merck’s broader bladder cancer program has already shown that pembrolizumab plus enfortumab vedotin can be delivered in perioperative settings, including in cisplatin-ineligible patients, though careful toxicity monitoring remains essential.
For clinicians, the key question will be whether the efficacy advantage is matched by acceptable perioperative tolerability and feasibility in routine practice. That is especially relevant in curative-intent disease, where treatment benefit must be weighed against operability, postoperative recovery, and long-term quality of life.
Results
The phase 3 KEYNOTE-B15/EV-304 trial demonstrated significant clinical benefit with perioperative pembrolizumab plus enfortumab vedotin compared with standard neoadjuvant chemotherapy in cisplatin-eligible MIBC:
- Event-free survival (EFS): 47% reduction in risk of recurrence, progression, or death (HR ~0.53)
- Overall survival (OS): ~35% reduction in risk of death
- Pathologic complete response (pCR): ~56% vs ~33% with chemotherapy
These findings show consistent improvement across key endpoints, supporting this combination as a potential new perioperative standard of care.
Why This Is a Bigger Story Than One Review Decision
This FDA action is part of a broader shift in genitourinary oncology.
Bladder cancer treatment is moving away from rigid stage-based silos and toward continuum-based strategies, where successful regimens can move from metastatic disease into earlier, potentially curable settings. Pembrolizumab plus enfortumab vedotin is one of the clearest examples of that transition.
It also reflects a larger trend in oncology: combinations built around checkpoint inhibition and ADCs are increasingly becoming candidates for perioperative use, not only metastatic control. In that sense, KEYNOTE-B15 is not just a bladder cancer story — it is part of the expanding role of modern systemic therapy in curative-intent care.
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