Pfizer Inc. (NYSE: PFE) – PADCEV and KEYTRUDA Priority Review has been officially granted by the U.S. Food and Drug Administration (FDA) for the perioperative treatment of adult patients with muscle-invasive bladder cancer (MIBC). This regulatory milestone, announced on April 20, 2026, marks a significant step toward expanding the use of this combination therapy beyond its current approval in the metastatic setting.
The supplemental Biologics License Application (sBLA) seeks approval for the combination of PADCEV (enfortumab vedotin-ejfv) and KEYTRUDA (pembrolizumab) to be used both before and after surgery (perioperative) in patients regardless of their eligibility for cisplatin-based chemotherapy. If approved, this regimen would become the first and only perioperative treatment available for this broad patient population.
Clinical Breakthrough: The EV-304/KEYNOTE-B15 Trial
The PADCEV and KEYTRUDA Priority Review is supported by robust data from the Phase 3 EV-304 (also known as KEYNOTE-B15) clinical trial. The study evaluated the combination against the current standard of care gemcitabine and cisplatin chemotherapy in patients with MIBC who were candidates for radical cystectomy.
The results demonstrated a statistically significant improvement in event-free survival (EFS) and overall survival (OS). Specifically, the combination reduced the risk of disease recurrence, progression, or death by 47% compared to traditional chemotherapy.
Superior Efficacy and Survival Outcomes
Under the PADCEV and KEYTRUDA Priority Review, the FDA will evaluate efficacy data that showed a median EFS that was not yet reached for the investigational arm, compared to 48.5 months for those receiving chemotherapy. Furthermore, the pathologic complete response (pCR) rate a key indicator of how well the tumor responds to neo-adjuvant therapy was significantly higher in the combination group.
Efficacy Results from Phase 3 EV-304 Trial
| Endpoint | PADCEV + KEYTRUDA (n=405) | Gemcitabine + Cisplatin (n=403) | Hazard Ratio (95% CI) / P-value |
| Median EFS | Not Reached | 48.5 Months | 0.53 (0.41–0.70); p < 0.0001 |
| 24-Month EFS Rate | 79.4% | 66.2% | — |
| 24-Month OS Rate | 86.9% | 81.3% | 0.65 (0.48–0.89); p = 0.0029 |
| pCR Rate | 55.8% | 32.5% | p < 0.0001 |
Safety Profile and Adverse Events
While the combination showed superior efficacy, the safety profile was consistent with previous trials of these two agents. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 75.7% of patients in the experimental arm. Common side effects of interest included skin reactions and peripheral neuropathy, which are characteristic of enfortumab vedotin.
Key Safety Data (Any Grade ≥3 TEAEs)
| Adverse Event Category | PADCEV + KEYTRUDA (%) | Chemotherapy (%) |
| Any Grade 3 or Higher TEAE | 75.7% | 67.2% |
| Skin Reactions | 63.5% (all grades) | — |
| Peripheral Neuropathy | 36.0% (all grades) | — |
| Treatment-Related Deaths | 0.5% (n=2) | 0.2% (n=1) |
