In the EV-302 study, patients treated with enfortumab vedotin and pembrolizumab showed a 55% lower risk of disease progression or death and a 53% lower risk of death compared to those receiving standard platinum-based chemotherapy. The study, involving 886 patients, found that the median progression-free survival was 12.5 months for the enfortumab vedotin and pembrolizumab arm versus 6.3 months for the chemotherapy arm. Overall survival also significantly favored the combination therapy, with a median of 31.5 months compared to 16.1 months for chemotherapy.
The combination therapy resulted in higher overall response rates, with a majority of responses ongoing at 12 and 18 months. These benefits were consistent across all prespecified subgroups, including those based on the presence of liver metastases, cisplatin eligibility, and PD-L1 expression status.
Treatment-related adverse events of grade 3 or higher were less frequent in the enfortumab vedotin and pembrolizumab arm (55.9%) compared to the chemotherapy arm (69.5%). Common adverse events included skin reactions, peripheral neuropathy, hyperglycaemia, severe skin reactions, pneumonitis, and hepatitis.
This study, published in The New England Journal of Medicine, is considered a landmark trial that sets a new standard-of-care regimen for locally advanced or metastatic urothelial cancer. However, the economic aspects of this treatment combination and its integration into healthcare systems remain important considerations for its broader application.
The research was supported by Astellas Pharma US, Merck Sharp and Dohme, and Seagen, which was acquired by Pfizer in December 2023.
