Padcev Plus Keytruda Approved as First-Line Treatment for Urothelial Cancer

The Food and Drug Administration (FDA) has granted accelerated approval to Padcev^® (enfortumab vedotin-ejfv) with Keytruda^® (pembrolizumab) for first-line treatment of adults with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-containing chemotherapy.

The approval was based on tumor response rate and durability of response observed in the multicohort (dose escalation cohort, cohort A, cohort K) phase 1b/2 EV-103 trial (ClinicalTrials.gov Identifier: NCT03288545), which included patients with la/mUC who did not receive prior systemic therapy and were not eligible for cisplatin-containing chemotherapy.

In the single-arm dose escalation cohort + cohort A, patients received enfortumab vedotin-ejfv with pembrolizumab. In cohort K, patients were randomly assigned to receive either the combination or enfortumab vedotin-ejfv alone. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

Among 121 patients who received enfortumab vedotin-ejfv plus pembrolizumab, the ORR was 68% (95% CI, 58.7-76.0), of which 12% achieved a complete response and 55% achieved a partial response. The median DOR for the dose escalation cohort + cohort A was 22.1 months (range: 1.0+ to 46.3+) and for cohort K was not reached (range, 1.2 to 24.1+).

The most common adverse reactions reported were increased glucose, increased aspartate aminotransferase, rash, decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased lymphocytes, fatigue, increased alanine aminotransferase, decreased sodium, increased lipase, decreased albumin, alopecia, decreased phosphate, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia, decreased potassium, decreased neutrophils, urinary tract infection, constipation, increased potassium, increased calcium, peripheral edema, dry eye, dizziness, arthralgia, and dry skin.  

Continued approval of this indication is contingent upon verification and description of clinical benefit from the ongoing phase 3 EV-302 confirmatory trial (ClinicalTrials.gov Identifier: NCT04223856).