ASCO 2021: Enfortumab Vedotin in Cisplatin-Ineligible Patients with Locally Advanced or Metastatic Urothelial Cancer Who Received Prior PD-1/PD-L1 Inhibitors: An Updated Analysis of EV-201 Cohort 2

( Approximately half of the patients with advanced urothelial carcinoma in the United States are cisplatin-ineligible. Of note, cisplatin-ineligible, platinum-naive patients with locally advanced or metastatic urothelial carcinoma who progress on or after anti-PD-1/L1 treatment have a poor prognosis and few treatment options. Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, demonstrated an overall survival benefit in patients with locally advanced or metastatic urothelial carcinoma who previously received anti-PD-1/L1 treatment and platinum-containing chemotherapy in EV-3011. EV-201 is a pivotal, single-arm, 2-cohort study. Cohort 2 enrolled cisplatin-ineligible patients with prior anti-PD-1/L1 treatment and no prior platinum for locally advanced or metastatic urothelial carcinoma. Previously presented (and now published) primary analysis results of EV-201 Cohort 2 included an overall response rate of 52% and a complete response rate of 20%, with a median duration of response of 10.9 months2. At the 2021 American Society of Clinical Oncology (ASCO) annual meeting, Dr. Bradley McGregor and colleagues presented updated results with three additional months of follow-up in which all responders were followed for ≥ 6 months after the onset of response.

In EV-201, patients received 1.25 mg/kg enfortumab vedotin on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed objective response rate per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, OS, and safety. The primary analysis data cutoff date was September 8, 2020, and the updated analysis cutoff date was December 4, 2020. The trial design for EV-201 is as follows:


There were 91 patients were enrolled and 89 were treated in Cohort 2; the median age was 75 years of age (range: 49-90). Patients were cisplatin-ineligible at baseline, primarily due to CrCl < 60 mL/min (78%). The primary tumor site was upper tract in 43%, and 79% had visceral metastases, including 24% with liver metastases. For the updated analysis, the median follow-up was 16.0 months and the median treatment duration was 6.0 months (range: 0.3-24.6). The confirmed objective response rate by blinded independent central review was 51% (95% CI 39.8-61.3), including 22% complete response among treated patients. The updated best overall response by blinded independent central review is as follows:


The updated objective response rate for subgroups by blinded independent review is as follows:


The median duration of response was 13.8 months (95% CI 6.4-not reached), median progression-free survival was 6.7 months (95% CI 5.0-8.3), and median overall survival was 16.1 months (95% CI 11.3-24.1). All-grade and grade ≥ 3 treatment-related adverse events were reported in 97% and 55% of patients, respectively. The most common all-grade treatment-related adverse events were alopecia (51%), peripheral sensory neuropathy (49%), and fatigue (34%). For treatment-related adverse events ≥ grade 3, each preferred term occurred in < 10% of patients. Treatment-related adverse events of interest included skin reactions (61% all grade, 17% ≥ grade 3), peripheral neuropathy (56% all grade, 8% ≥ grade 3), and hyperglycemia (10% all grade, 6% ≥ grade 3). Four deaths were previously reported as treatment-related by investigators: 3 events in less than 30 days of first enfortumab vedotin dose (acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome) and one greater than 30 days of last enfortumab vedotin dose (pneumonitis).

Dr. McGregor concluded his presentation of the EV-201 updated analysis with the following take-home messages:

  • Cisplatin-ineligible patients need effective treatment options following immunotherapy
  • Efficacy and safety in this updated analysis of EV-201 Cohort 2 are consistent with the primary analysis
  • The majority of platinum-naive, cisplatin-ineligible locally advanced or metastatic urothelial carcinoma patients who progressed on/after anti-PD-1/L1 treatment responded to enfortumab vedotin, with 22% achieving complete response and median duration of response exceeding a year
  • Progression-free survival and OS continue to be encouraging in this elderly population, with no new safety signals
  • These data show the potential for enfortumab vedotin as a non-platinum option for cisplatin-ineligible patients following anti-PD-1/L1 treatment

Clinical trial information: NCT03219333

Presented By: Bradley A. McGregor, MD, Dana-Farber Cancer Institute, Boston, MA

Written By: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 America Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021 

  1. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021 Mar 25;384(12):1125-1135.
  2. Yu EY, Petrylak DP, O’Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 May 12;S1470-2045(21)00094-2.