Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy Journal Article


Authors: Rosenberg, J. E.; O'Donnell, P. H.; Balar, A. V.; McGregor, B. A.; Heath, E. I.; Yu, E. Y.; Galsky, M. D.; Hahn, N. M.; Gartner, E. M.; Pinelli, J. M.; Liang, S. Y.; Melhem-Bertrandt, A.; Petrylak, D. P.
Article Title: Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy
Abstract: PURPOSELocally advanced or metastatic urothelial carcinoma is an incurable disease with limited treatment options, especially for patients who were previously treated with platinum and anti?programmed death 1 or anti?programmed death ligand 1 (PD-1/L1) therapy. Enfortumab vedotin is an antibody?drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma.METHODSEV-201 is a global, phase II, single-arm study of enfortumab vedotin 1.25 mg/kg (intravenously on days 1, 8, and 15 of every 28-day cycle) in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum chemotherapy and anti?PD-1/L1 therapy. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review. Key secondary end points were duration of response, progression-free survival, overall survival, safety, and tolerability.RESULTSEnfortumab vedotin was administered to 125 patients with metastatic urothelial carcinoma. Median follow-up was 10.2 months (range, 0.5 to 16.5 months). Confirmed objective response rate was 44% (95% CI, 35.1% to 53.2%), including 12% complete responses. Similar responses were observed in prespecified subgroups, such as those patients with liver metastases and those with no response to prior anti?PD-1/L1 therapy. Median duration of response was 7.6 months (range, 0.95 to 11.30+ months). The most common treatment-related adverse events were fatigue (50%), any peripheral neuropathy (50%), alopecia (49%), any rash (48%), decreased appetite (44%), and dysgeusia (40%). No single treatment-related adverse events grade 3 or greater occurred in 10% or more of patients.CONCLUSIONEnfortumab vedotin demonstrated a clinically meaningful response rate with a manageable and tolerable safety profile in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and anti?PD-1/L1 therapies.
Keywords: cisplatin; chemotherapy; multicenter; eortc; cancer; nectin-like molecules
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 29
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-10-10
Start Page: 2592
End Page: 2600
Language: English
ACCESSION: WOS:000491485600002
DOI: 10.1200/jco.19.01140
PROVIDER: wos
PMCID: PMC6784850
PUBMED: 31356140
Notes: Source: Wos
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  1. Jonathan Eric Rosenberg
    282 Rosenberg