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Real-world Effectiveness of Single-Agent Enfortumab Vedotin in Patients With Advanced Urothelial Carcinoma

Background: Enfortumab vedotin (EV) is a nectin-4-directed antibody and microtubule inhibitor conjugate indicated for patients with metastatic urothelial carcinoma (mUC) who have received prior platinum-based chemotherapy and PD-1/L1 inhibitors or are ineligible for cisplatin-containing regimens and have undergone at least 1 prior line of therapy. EV is also indicated in combination with pembrolizumab in the first-line setting. However, real-world effectiveness of EV based on treatment line and impact of prior therapy remains unclear.

Methods: This retrospective study utilized the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients with advanced, recurrent, or mUC of upper or lower urinary tract who received single-agent EV in the second-line or beyond after December 18, 2019 (FDA accelerated approval date), were included. Patients without documentation of first-line therapy or without evidence of contact for 90 days from mUC diagnosis were excluded. Time to next therapy (TTNT) and overall survival (OS) were analyzed based on treatment line and prior platinum-based chemotherapy and PD-1/L1 inhibitors using Kaplan-Meier survival estimates and its 95% confidence interval.

Results: Between January 17, 2020, and September 30, 2022, 6566 patients with mUC received systemic treatment, with 431 receiving EV. EV monotherapy was administered across various lines (N = 371): second (157), third (132), fourth (62), and fifth (20). Approximately 22% of patients had prior platinum-based therapy, and 48% had prior PD-1/L1 inhibitors. Median TTNT and OS varied across treatment lines, with patients with prior platinum exposure generally showing longer TTNT and OS, notably in those receiving EV in the fourth-line setting.

Conclusions: EV demonstrates efficacy in patients with mUC regardless of prior receipt of platinum-based chemotherapy and PD-1/L1 inhibitors or treatment line. While only hypothesis-generating, these findings provide valuable insights for patient counseling, prognostication, and therapeutic decision-making in clinical practice.
Nicolas Sayegh ,1 Yeonjung Jo,2 Georges Gebrael,3 Nishita Tripathi,4 Beverly Chigarira,3 Ayana Srivastava,3 Blake Nordblad,3 Emre Dal,3 Chadi Hage Chehade,3 Jon Mahlow,3 Benjamin L Maughan,3 Sumati Gupta,3 Neeraj Agarwal,3 Umang Swami5

  1. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Department of Internal Medicine, University of Texas Southwestern, Dallas, TX.
  2. Division of Biostatistics, Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT; Cancer Biostatistics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
  3. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
  4. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Department of Internal Medicine, Wayne State University, Detroit, MI.
  5. Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. 

Source: Sayegh N, Jo Y, Gebrael G, Tripathi N, Chigarira B, Srivastava A, Nordblad B, Dal E, Hage Chehade C, Mahlow J, Maughan BL, Gupta S, Agarwal N, Swami U. Real-world Effectiveness of Single-Agent Enfortumab Vedotin in Patients With Advanced Urothelial Carcinoma. Clin Genitourin Cancer. 2025 Feb;23(1):102287. doi: 10.1016/j.clgc.2024.102287. Epub 2024 Dec 6. PMID: 39721833; PMCID: PMC11757033.