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Two new analyses further bolster the groundbreaking data that rapidly shifted the combination of enfortumab vedotin (EV) plus pembrolizumab into the forefront for treating patients with advanced urothelial cancer.
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In the landmark phase 3 EV-302/KEYNOTE-A39 randomized trial of 886 patients with locally advanced or metastatic urothelial carcinoma, the antibody-drug conjugate / immune checkpoint inhibitor combination doubled progression-free survival (PFS) and overall survival (OS) compared to standard chemotherapy. Since those data were first reported in December 2023, EV-pembrolizumab has replaced chemotherapy as the preferred first-line treatment for patients with advanced urothelial cancer.
Now, a new pre-specified analysis shows positive patient-reported outcomes with EV-pembrolizumab, and in an exploratory analysis, patient response to the combination was independent of baseline Nectin-4 and programmed death ligand 1 (PDL-1) expression.
“This new regimen is the cancer advance of the century for patients with urothelial cancer. We have further shown that EV-pembrolizumab does not worsen patients’ quality of life, and that they benefit regardless of their sites of metastases and level of nectin-4 expression or PD-L1 in their tumors, says Shilpa Gupta, MD, Director of Genitourinary Medical Oncology at Cleveland Clinic Cancer Institute and a co-author of the study.
Dr. Gupta presented the data on patient-reported outcomes earlier this year at the 2024 American Society of Clinical Oncology meeting. In the 128 patients with moderate-to-severe pain at baseline who were treated with EV-pembrolizumab, there was a meaningful improvement on the Brief Pain Inventory of worst pain. “Assessment with the Global Health Status / Quality of Life scale developed by the European Organization for Research and Treatment of Cancer (EORTC) revealed that in patients treated with EV-pembrolizumab, there was no detriment to their well-being. And in Global Health Status scores, we saw clinically meaningful improvement over chemotherapy, which is huge. Notably, we collected patient-reported outcomes throughout their entire journeys, not just during treatment” Gupta says.
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High levels of Nectin-4, the cell adhesion molecule that EV targets, were present in nearly all of the 800 available patient tumor samples, with 89% having Nectin-4 H scores above 150.
Importantly, patients who received EV-pembrolizumab had consistently improved PFS, OS and and objective response rate compared to chemotherapy, regardless of Nectin-4 expression H scores <275 or ≥275, and had consistent PFS and OS benefits, regardless of Nectin-4 and PDL-1 expression.
“This just confirms that you don’t need to worry about whether Nectin-4 or PD-L1 is high or not. You don’t need to measure it,” Gupta says. “This new regimen offers a beacon of hope to patients with urothelial cancer worldwide and we hope to see it become accessible and affordable globally.”
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