FDA Approves Enfortumab and Pembrolizumab for Urothelial Cancer in an advanced or metastatic stage

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY


The U.S. Food and Drug Administration gave its approval for the use of enfortumab vedotin-ejfv (Padcev, Astellas Pharma) in combination with pembrolizumab (Keytruda, Merck) as a treatment for patients diagnosed with urothelial carcinoma in an advanced or metastatic stage (la/mUC) on December 15, 2023. This combination had previously received accelerated approval from the FDA for its use in treating
la/mUC patients who cannot tolerate cisplatin-based chemotherapy.


Study ID number: NCT04223856


Approval was based on EV-302/KN-A39, an open-label, randomized trial that included 886 patients with la/mUC and no prior systemic therapy for advanced disease. Patients were split into two groups: one received a combination of enfortumab and pembrolizumab, and the other received platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). The suggested dose for enfortumab vedotin-ejfv, when paired with pembrolizumab, is 1.25 mg/kg given via a 30-minute IV infusion on the first and eighth days of a 21-day cycle until the disease worsens or side effects become too severe. Pembrolizumab, when used with enfortumab vedotin-ejfv, is recommended at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks. This continues until the disease worsens, side effects are too severe, or after two years of treatment.


Efficacy was established on overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central review. Statistically significant improvements in both OS and PFS were demonstrated for enfortumab vedotin-ejfv with pembrolizumab compared with platinum-based chemotherapy. Results of the study indicate median OS of 31.5 months (95% CI: 25.4, not estimable) for
patients treated with the combination of enfortumab vedotin-ejfv and pembrolizumab compared to 16.1 months (95% CI: 13.9, 18.3) for those treated with standard platinum-based chemotherapy (Hazard ratio [HR] 0.47 [95% CI: 0.38, 0.58]; p-value<0.0001). Likewise, there was significant improvement in PFS as well when compared between these two groups (HR 0.45 [95% CI: 0.38, 0.54]; p-value<0.0001).


Patients receiving enfortumab vedotin-ejfv with pembrolizumab often experienced various side effects. These included changes in blood chemistry, fatigue, weight and appetite loss, skin reactions like rash
and itching, hair loss, changes in taste, urinary tract infections, and decreases in certain blood cells. Specific changes in blood chemistry involved increases in aspartate aminotransferase, creatinine,
glucose, lipase, urate, and potassium, and decreases in lymphocytes, hemoglobin, sodium, phosphate, albumin, neutrophils, and platelets. Other notable side effects were peripheral neuropathy and dry


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