ASCO 2019: EV-201: Results of Enfortumab Vedotin Monotherapy for Locally Advanced or Metastatic Urothelial Cancer Previously Treated with Platinum and Immune Checkpoint Inhibitors - Medical Oncologist Perspective

Chicago, IL (UroToday.com) After cisplatin-based chemotherapy and immune checkpoint inhibitors, there exist a paucity of effective therapies for patients with metastatic urothelial carcinoma (mUC). Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) which delivers a microtubule-disrupting agent to tumors expressing Nectin-4, a protein overexpressed in urothelial, breast, pancreatic, lung, and esophageal cancer.1
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In the phase I EV-101 study of enfortumab vedotin, 112 patients received EV, the majority of whom received prior platinum chemotherapy (81%) and a checkpoint inhibitor (75%) and this patient population had an objective response rate of 33%. The median overall survival (OS) was reported to be 12.5 months.2 In this study, the authors describe the results of EV-201, EV monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.
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This abstract provides data on Cohort 1 of the study above. 125 patients were enrolled and the maximum time on treatment is 15.6 months and ongoing. Eligibility criteria are shown below.
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Of note, nectin expression was NOT mandated in the study but was measured for all patients and could be detected in ALL patients.
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125 patients were enrolled and 16% of patients continue on treatment. The median time of treatment was 4.6 months and 53% of patients have discontinued due to the progression of disease.
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Baseline characteristics are typical of this population of patients with mUC. Of note, 42% of patients had 2 or more Bellmunt adverse prognostic factors and 27% of patients were 75 or older. 35% of patients had upper tract disease.
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In terms of response, 44% of patients had a confirmed objective response, with a 12% complete response (CR) rate.
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84% of all patients had tumor shrinkage.
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In terms of progression-free survival (PFS) and overall survival (OS), the median OS is 11.7 months in this phase 2 with a PFS of 5.8 months.
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In terms of AEs, 12% of patients discontinued due AEs, with the most common reason being neuropathy. There was one
treatment-related death but this was in a patient with ILD on high dose steroids who may have had PCP pneumonia. The most common grade 3 AEs were fatigue, anemia, and neutropenia.
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In this single-arm phase II study, enfortumab vedotin shows promising anti-tumor activity in an unselected population of patients with mUC who have had either prior PD-1/L1 or prior platinum therapy. This was a high-risk population, many with visceral metastases, and despite this enfortumab showed great efficacy with a 12% CR rate.  We look forward to seeing the data in cohort-2, which will include cisplatin-ineligible patients as well as data from EV-301, the randomized phase 3 study comparing enfortumab to standard of care post-platinum.
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Presented by: Daniel Peter Petrylak, MD, Yale Cancer Center, New Haven, CT 

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody–drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer research 2016;76:3003-13.
  2. Rosenberg JE, Sridhar SS, Zhang J, et al. Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). American Society of Clinical Oncology; 2018.
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