Enhanced Antitumor Activity against Urothelial Carcinoma with the Enfortumab Vedotin and Pembrolizumab Combination
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 12th, 2024
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Platinum-based chemotherapy has long been the conventional therapy for urothelial carcinoma, but its efficacy remains limited, resulting in a low 5-year survival rate. Recent investigations have shown promising outcomes with the combination of enfortumab vedotin, an antibody targeting nectin-4 - a cell adhesion molecule overexpressed on tumor cells - and pembrolizumab, a PD-1 inhibitor. In light of these findings, a larger-scale study was undertaken to evaluate the enhanced antitumor activity of the enfortumab vedotin and pembrolizumab combination against urothelial carcinoma.
The study enrolled 886 patients diagnosed with unresectable advanced or metastatic urothelial carcinoma, with an average age of 69 years old, of which approximately 70% had tumors originating in the lower urinary tract. Patients were randomly allocated to receive either the enfortumab vedotin-pembrolizumab combination or the current standard chemotherapy regimen on a 3-week cycle. Enfortumab vedotin was intravenously infused at a dose of 1.25 mg per kilogram of body weight on the 1st and 8th day of the cycle, and pembrolizumab was intravenously administered at a dose of 200 mg on the 1st day of the cycle. Patients in the standard chemotherapy group received gemcitabine intravenously at a dose of 1000 mg per square meter of body-surface area on the 1st and 8th day of the cycle, along with either intravenous cisplatin or intravenous carboplatin on the 1st day of the cycle. Following a mean follow-up duration of 17.2 months, the researchers observed a 55% reduction in the risk of disease progression and death with the enfortumab vedotin-pembrolizumab combination. Additionally, this combination therapy delayed disease progression by 12.5 months and prolonged survival by 31.5 months, significantly longer than the reported 6.3 months and 16.1 months, respectively.
The study enrolled 886 patients diagnosed with unresectable advanced or metastatic urothelial carcinoma, with an average age of 69 years old, of which approximately 70% had tumors originating in the lower urinary tract. Patients were randomly allocated to receive either the enfortumab vedotin-pembrolizumab combination or the current standard chemotherapy regimen on a 3-week cycle. Enfortumab vedotin was intravenously infused at a dose of 1.25 mg per kilogram of body weight on the 1st and 8th day of the cycle, and pembrolizumab was intravenously administered at a dose of 200 mg on the 1st day of the cycle. Patients in the standard chemotherapy group received gemcitabine intravenously at a dose of 1000 mg per square meter of body-surface area on the 1st and 8th day of the cycle, along with either intravenous cisplatin or intravenous carboplatin on the 1st day of the cycle. Following a mean follow-up duration of 17.2 months, the researchers observed a 55% reduction in the risk of disease progression and death with the enfortumab vedotin-pembrolizumab combination. Additionally, this combination therapy delayed disease progression by 12.5 months and prolonged survival by 31.5 months, significantly longer than the reported 6.3 months and 16.1 months, respectively.