First-line enfortumab vedotin (EV) plus pembrolizumab significantly improved survival in patients with locally advanced or metastatic urothelial cancer.
Previous studies combining chemotherapy concurrently with immunotherapy have failed to improve survival in locally advanced or metastatic urothelial cancer patients [1,2]. Recently, the antibody-drug conjugate EV demonstrated a survival benefit in previously treated patients with locally advanced or metastatic urothelial cancer [3].
The phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) explored the efficacy and safety of first-line EV combined with pembrolizumab. The initial results were presented by Dr. Thomas Powles (Queen Mary University of London, UK) [4].
A total of 886 participants with previously untreated locally advanced or metastatic urothelial cancer were randomly assigned 1:1 to first-line EV/pembrolizumab until progression (maximum 35 cycles of pembrolizumab) or 6 cycles platinum-based chemotherapy (maintenance avelumab permitted). The primary endpoints were PFS and OS.
EV/pembrolizumab strongly improved both PFS and OS. Median PFS was 12.5 months versus 6.3 months (HR, 0.45; 95% CI, 0.38-0.54; P<0.00001) and median OS was 31.5 months versus 16.1 months (HR, 0.47; 95% CI, 0.38-0.58; P<0.00001) in the EV/pembrolizumab arm and chemotherapy arm, respectively. EV/pembrolizumab also outperformed chemotherapy in overall response rate (ORR; 67.7% vs 44.4%). Moreover, the complete response rate more than doubled: 29.1% versus 12.5%. The rate of adverse events in grade ≥3 was highest in the chemotherapy arm, amounting to 70% versus 56% in the EV/pembrolizumab arm. “This is the first time we have beaten chemotherapy in the first line,” said Dr. Powles.
Based on these results, Dr. Powles concluded that EV/pembrolizumab has raised the bar for OS in locally advanced or metastatic urothelial cancer, showing a significant decrease in the chance of progression and death. “These results support EV/pembrolizumab to become the new first-line standard of care.”
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