FDA Approves Enfortumab Vedotin, Pembrolizumab for Treatment of Urothelial Cancer


The approval marks the first for an alternative to platinum-containing chemotherapy.

The FDA has approved enfortumab vedotin-ejfv (Padcev; Astellas Pharma Inc; Pfizer Inc) combined with pembrolizumab (Keytruda; Merck and Co) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC), according to a press release from Astellas.

3d rendered illustration of the anatomy of a cancer cell | Image Credit: SciePro - stock.adobe.com

SciePro - stock.adobe.com

The combination's approval marks the first for an alternative to platinum-containing chemotherapy, the current standard of care for first-line treatment of la/mUC. Additionally, this is the first and only approval of an antibody-drug conjugate and programed cell death protein 1 (PD-1) inhibitor.

"Today's FDA approval represents a paradigm change in the treatment of advanced bladder cancer and provides hope to the thousands of Americans impacted by this aggressive disease. This achievement is notable, as it is the first regimen approved in advanced [UC] that has demonstrated superiority to platinum chemotherapy, the gold standard of care for decades,” Ahsan Arozullah, MD, MPh, senior vice president and head of oncology development at Astellas, said in the press release.

The approval was based on results from the phase 3 EV-302 clinical trial, also named the KEYNOTE-A39 trial, demonstrating that the combination doubled median overall survival (OS) and median progression-free survival (PFS) when compared to the standard of care. The trial was a confirmatory trial used for the accelerated approval of the combination in the United States, which was initially approved in April 2023 for individuals with la/mUC who are not eligible to received cisplatin-contain chemotherapy as well as expanding the label to include those who are eligible to receive cisplatin chemotherapy.

About The EV-302 Trial

Trial Name: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

ClinicalTrial.gov ID: NCT04223856

Sponsor: Astellas Pharma Global Development Inc

Completion Date: August 2023

“The overall survival benefit seen in the EV-302 trial demonstrates the potential for Padcev in combination with pembrolizumab to impact first-line treatment of patients with [la/mUC]. In my opinion, this is a meaningful advancement over platinum-based chemotherapy in the systemic treatment of these patients,” Thomas Powles, MRCP, MD, professor of genitourinary oncology at the Queen Mary University of London, said in a press release.

The trial included 886 individuals who were previously treated for la/mUC and were eligible for cisplatin- or carboplatin-containing chemotherapy, regardless of programmed cell death ligand-1 (PD-L1) status. The individuals in the study received either enfortumab vedotin-ejfv in combination with pembrolizumab or chemotherapy. Secondary endpoints included objective response rate and duration of response.

Meeting the dual primary endpoints of OS and PFS, the combination resulted in 31.5 months and 12.5 months, respectively, compared with 16.1 months and 6.3 months, respectively. There was a reduction in the risk of death of 53% and reduction in the risk of cancer progression or death of 55%, according to the press release.

In the subgroups of those who were cisplatin eligible and those who were ineligible, there was a 47% and 57% reduced risk of death, respectively, and a 52% and 57% risk of progression or death, respectively. For the PD-L1 and high PD-L1 expression subgroups, there was a 56% and 51% reduced risk of death, respectively, and a 50% and 58% reduced risk of progression or death, respectively, according to the press release.

The most common all-grade adverse events included laboratory abnormalities, which were related to treatment with the combination. These included increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, and more. The press release stated that the safety results of the trial were consistent with those previously reported for the combination, and no new safety issues were identified.


Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) approved by FDA as the first and only ADC plus PD-1 to treat advanced bladder cancer. News release. Astellas Pharma. December 15, 2023. Accessed December 18, 2023. https://newsroom.astellas.us/2023-12-15-PADCEV-R-enfortumab-vedotin-ejfv-with-KEYTRUDA-R-pembrolizumab-Approved-by-FDA-as-the-First-and-Only-ADC-Plus-PD-1-to-Treat-Advanced-Bladder-Cancer

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