ESMO Virtual Congress 2020: Long-Term Results of Enfortumab Vedotin Monotherapy for Locally Advanced or Metastatic Urothelial Cancer in the EV-201 Study in Patients Previously Treated with Platinum and PD-1/PD-L1 Inhibitors

( It is well-known that locally advanced and metastatic urothelial carcinoma is an incurable disease with poor overall survival (OS), especially in patients who progress on or after platinum-containing chemotherapy.

Taxanes/vinflunine showed a median OS of 7.4 months and a 12-month OS rate of 30.7% in patients who previously received platinum‑containing therapy.1 Currently, OS data after treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy is limited.

In the EV-201 study (NCT03219333; EudraCT Number 2017-003479-78), enfortumab vedotin, which is an antibody-drug conjugate, demonstrated an objective response rate (ORR) of 44% in Cohort 1, that consisted of patients who previously received both a prior PD-1/PD-L1 inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant or locally-advanced/metastatic setting.2

In December 2019, the US FDA approved the use of enfortumab vedotin based on the data from the EV-201 Cohort 1. In this presented poster, the authors present updated OS and safety data from EV-201 Cohort 1 with an additional one year of follow-up.

Enfortumab vedotin is directed against Nectin-4, which is a cell surface adhesion protein found on target cells, and upon internalization, releases monomethyl auristatin E, resulting in cell cycle arrest and apoptotic cell death (Figure 1). The study scheme of EV-201 cohort one is shown in Figure 2.

Figure 1: Enfortumab vedotin mechanism:


Figure 2 – EV-201 cohort 1 study scheme:


The key eligibility criteria for the EV-201 study are shown in table 1, the patient disposition is shown in table 2, and patient demographics and clinical characteristics are shown in table 3.

Table 1 – Key eligibility criteria:


Table 2 – Patient disposition:


Table 3- Patient demographics and clinical characteristics:


As can be clearly seen, the analyzed patients with advanced urothelial carcinoma were predominantly older males, with the majority being ECOG 1, and their primary site of disease was in the lower urinary tract. The number of median previous treatment lines were 3. Most of the patients had poor prognostic factors, with 90% having visceral disease, and 40% had liver metastases.

Figure 1 showed Kaplan Meyer estimates of survival with a 12-month OS rate of 50.4%. The treatment-related adverse events are shown in Figure 2, showing that the most common adverse events were alopecia, fatigue, and decreased appetite. There were a few discontinuations due to treatment-related AEs (12%). There was one treatment-related death reported by the investigator.

Figure 1 – Kaplan Meyer estimates of survival:


Figure 2 – Treatment related adverse events:


In conclusion, based on this long-term follow-up of EV-201 Cohort 1, the median OS was 12.4 months (95% CI: 9.46, 15.57), with a median follow-up of 22.3 months. At key milestones of 12 and 18 months, one-half and approximately one-third of patients, respectively, were alive. Enfortumab vedotin was tolerable with a manageable safety profile consistent with previous reports.

Presented by: Peter O'Donnell, MD, Associate Professor of Medicine, Department of Medicine, University of Chicago Medicine, Chicago, Illinois

Written by: Hanan Goldberg, MD, MSc., Assistant Professor of Urology, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.


  1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. New England Journal of Medicine 2017; 376(11): 1015-26.
  2. Rosenberg JE, O'Donnell PH, Balar AV, et al. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2019; 37(29): 2592-600.
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