The US Food and Drug Administration (FDA) approved enfortumab vedotin-ejfv (Padcev, Astellas Pharma) in combination with pembrolizumab (Keytruda) to treat locally advanced or metastatic urothelial cancer.
The FDA previously approved the combination in April 2023 for patients who are ineligible for first-line cisplatin-based chemotherapy. The expanded indication makes the combination the first approved alternative to chemotherapy for all patients with locally advanced or metastatic urothelial cancer.
Approval of the new indication was based on the EV-302/KEYNOTE-A39 open-label trial, which randomly assigned 886 patients with locally advanced or metastatic urothelial cancer and no prior systemic therapy 1:1 to either enfortumab vedotin with pembrolizumab or platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
Median overall survival was nearly twofold longer for patients receiving enfortumab vedotin: 31.5 months vs 16.1 months in the chemotherapy arm. Median progression-free survival (PFS) was also about two times longer in the enfortumab vedotin–plus-pembrolizumab group: 12.5 vs 6.3 months.
Consistent overall survival and PFS results were observed across predefined subgroups, including cisplatin eligibility and PD-L1 expression level.
The most common adverse reactions with the combination, occurring in at least 20% of patients, included increased aspartate aminotransferase, creatinine, rash, glucose, and lipase as well as decreased lymphocytes and hemoglobin, and peripheral neuropathy.
The recommended enfortumab vedotin dose with pembrolizumab is 1.25 mg/kg IV, up to a maximum of 125 mg, on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. The recommended pembrolizumab dose with the combination is 200 mg IV every 3 weeks or 400 mg every 6 weeks for up to 2 years.
M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.
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