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      Call for Papers: Digital Diagnostic Techniques

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      About Pathobiology: 3.5 Impact Factor I 8.5 CiteScore I 1.088 Scimago Journal & Country Rank (SJR)

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      Two Cases of Exacerbation of Asthma during Treatment with Enfortumab Vedotin

      case-report

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          Abstract

          Enfortumab vedotin is an antibody-drug conjugate against nectin-4 that is recently being used in the management of patients with urothelial carcinoma. The common adverse events include rashes, peripheral neuropathy, and hyperglycemia. Only a few cases of associated respiratory symptoms have been reported. Herein, we describe 2 patients with advanced urothelial carcinoma who experienced asthma exacerbation after initiating enfortumab vedotin treatment. Both patients improved with inhalation therapy. Since nectin-4 is expressed in the tracheal epithelium, its association with asthma is likely. This study highlights that clinicians should caution patients with a history of asthma against the worsening of respiratory symptoms when enfortumab vedotin is administered.

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          Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma

          Thomas Powles, Jonathan E Rosenberg, Guru P. Sonpavde … (2021)
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            Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy

            Jonathan E Rosenberg, Peter H. O’Donnell, Arjun V Balar … (2019)
            PURPOSE Locally 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. METHODS EV-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. RESULTS Enfortumab 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. CONCLUSION Enfortumab 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.
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              Adherens junction protein nectin-4 (PVRL4) is the epithelial receptor for measles virus

              Michael D. Mühlebach, Mathieu Mateo, Patrick Sinn … (2011)
              Measles (MV) is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths 1,2 . While it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to initially infect macrophages and dendritic cells of the airways using the signaling lymphocytic activation molecule (SLAM, CD150) as receptor 3-6 . These cells then cross the respiratory epithelium and ferry the infection to lymphatic organs where MV replicates vigorously 7 . How and where the virus crosses back into the airways has remained unknown. Based on functional analyses of surface proteins preferentially expressed on virus-permissive epithelial cell lines, we identified nectin-4 8 (poliovirus-receptor-like-4) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains MV entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is down-regulated in infected epithelial cells, including those of macaque tracheas. While other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that MV targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer 9-11 , which has implications for ongoing MV-based clinical trials of oncolysis 12 .
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                Author and article information

                Journal
                Journal ID (nlm-ta): Case Rep Oncol
                Journal ID (iso-abbrev): Case Rep Oncol
                Journal ID (hwp): CRO
                Journal ID (publisher-id): CRO
                Title: Case Reports in Oncology
                Publisher: S. Karger AG (Basel, Switzerland )
                ISSN (Electronic): 1662-6575
                Publication date (Electronic): 25 October 2023
                Publication date Collection: Jan-Dec 2023
                Publication date PMC-release: 25 October 2023
                Volume: 16
                Issue: 1
                Pages: 1217-1222
                Affiliations
                [a ]Department of Pharmacy, Kariya Toyota General Hospital, Kariya, Japan
                [b ]Department of Urology, Kariya Toyota General Hospital, Kariya, Japan
                [c ]Department of Respiratory Medicine, Kariya Toyota General Hospital, Kariya, Japan
                Author notes
                Correspondence to: Takamasa Homma, takamasahom@ 123456gmail.com
                Article
                Publisher ID: 534150
                DOI: 10.1159/000534150
                PMC ID: 10601777
                PubMed ID: 37900848
                SO-VID: caa95447-cb3c-4377-97b6-fea33f613e84
                Copyright © © 2023 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 10 August 2023
                Date accepted : 11 September 2023
                Date: 2023
                Page count
                Figures: 3, References: 17, Pages: 6
                Funding
                This study has not received specific funding from any public, commercial, or non-profit sector funding agencies.
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: enfortumab vedotin,urothelial carcinoma,asthma,nectin-4,antibody-drug conjugate
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: enfortumab vedotin, urothelial carcinoma, asthma, nectin-4, antibody-drug conjugate

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