Padvec Prolongs Survival in Locally Advanced or Metastatic Urothelial Carcinoma

Urothelial carcinoma is the sixth most common type of cancer and it accounts for about 90% of the cases of bladder cancer.(Urothelial cancers arise out of the urothelium that lines the structures of the urinary tract, so they can also occur in the ureters and the kidneys although most occur in the bladder.) Unfortunately, many patients develop advanced muscle-invasive or metastatic disease resulting in poor clinical outcomes with 5%-15% survival rates.Platinum-based chemotherapy is considered the first-line treatment for advanced urothelial carcinoma, but resistance to these therapies is a problem.

In a recent industry-funded study published in the New England Journal of Medicine, Padvec (enfortumab vedotin), a novel drug that specifically targets cancer cells, was evaluated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-containing chemotherapy and had disease progression during or after treatment with a programmed death receptor-1or programmed death-ligand 1 inhibitor.

Padcev received FDA approval December 18, 2019 for patients with advanced urothelial cancer whose disease has progressed on chemotherapy and immunotherapy. The drug is marketed and distributed by Seagen, which was previously known as Seattle Genetics.

Seagen and Astellas Pharma, a Japanese biotech company, announced that they had submitted two supplemental Biologics License Applications for Padcev that were based on the results reported in the New England Journal of Medicine.

The trial, dubbed EV-301, was a global, open-label, phase 3 trial that set out to measure the clinical benefit of Padcev compared with standard chemotherapy to assess the primary endpoint of survival in patients with urothelial carcinoma with disease progression despite treatment with other therapies. Padvec was administered at a dose of 1.25 mg/kg of body weight by intravenous infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle.There were 608 patients randomized across 19 countries to receive Padcev (301 patients) or chemotherapy (307 patients).The median age of study participants was 68 years (range 30-88), and 77.3% of the patients were men.

A total of 301 deaths that occurred at the time of the interim analysis (134 in the Padvec group and 167 in the chemotherapy group). The risk of death was 30% lower with Padvec than with chemotherapy after a median follow-up of 11.1 months.

One study limitation is that more men than women were included in the study, although that is probably because that men are more at risk of developing urothelial carcinoma. This study demonstrates that there was a significantly longer overall survival with Padcev than with standard chemotherapy and further highlights the important role this novel therapy plays in advanced urothelial cancer.