Cargando…

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients

Enfortumab vedotin (EV), an antibody–drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Th...

Descripción completa

Detalles Bibliográficos
Autores principales: Vulsteke, Christof, De Cocker, Laurens, Gómez de Liaño, Alfonso, Montesdeoca, Cristina, De Meulenaere, Astrid, Croes, Lieselot, Delombaerde, Danielle, Szabados, Bernadett, Powles, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057070/
https://www.ncbi.nlm.nih.gov/pubmed/36986475
http://dx.doi.org/10.3390/ph16030375
_version_ 1785016273051058176
author Vulsteke, Christof
De Cocker, Laurens
Gómez de Liaño, Alfonso
Montesdeoca, Cristina
De Meulenaere, Astrid
Croes, Lieselot
Delombaerde, Danielle
Szabados, Bernadett
Powles, Thomas
author_facet Vulsteke, Christof
De Cocker, Laurens
Gómez de Liaño, Alfonso
Montesdeoca, Cristina
De Meulenaere, Astrid
Croes, Lieselot
Delombaerde, Danielle
Szabados, Bernadett
Powles, Thomas
author_sort Vulsteke, Christof
collection PubMed
description Enfortumab vedotin (EV), an antibody–drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published yet regarding the effect of EV on brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old white male patient, who had been heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. After three cycles, the first evaluation showed a partial remission by RECIST v1.1, with a near complete response on the brain metastasis and disappearance of neurological symptoms. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and avelumab in maintenance. The patient achieved a complete response and received therapy for five months. Nevertheless, therapy was discontinued at the patient’s request. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old white male patient also received EV after previous progression on cisplatin–gemcitabine and atezolizumab maintenance, followed by palliative whole-brain radiotherapy and two cycles of vinflunine. After three cycles of EV, there was a significant reduction in the brain metastases. The patient is currently still receiving EV. These are the first reports on the efficacy of EV in patients with urothelial carcinoma and active brain metastases.
format Online
Article
Text
id pubmed-10057070
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100570702023-03-30 First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients Vulsteke, Christof De Cocker, Laurens Gómez de Liaño, Alfonso Montesdeoca, Cristina De Meulenaere, Astrid Croes, Lieselot Delombaerde, Danielle Szabados, Bernadett Powles, Thomas Pharmaceuticals (Basel) Case Report Enfortumab vedotin (EV), an antibody–drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published yet regarding the effect of EV on brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old white male patient, who had been heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. After three cycles, the first evaluation showed a partial remission by RECIST v1.1, with a near complete response on the brain metastasis and disappearance of neurological symptoms. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and avelumab in maintenance. The patient achieved a complete response and received therapy for five months. Nevertheless, therapy was discontinued at the patient’s request. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old white male patient also received EV after previous progression on cisplatin–gemcitabine and atezolizumab maintenance, followed by palliative whole-brain radiotherapy and two cycles of vinflunine. After three cycles of EV, there was a significant reduction in the brain metastases. The patient is currently still receiving EV. These are the first reports on the efficacy of EV in patients with urothelial carcinoma and active brain metastases. MDPI 2023-03-01 /pmc/articles/PMC10057070/ /pubmed/36986475 http://dx.doi.org/10.3390/ph16030375 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Vulsteke, Christof
De Cocker, Laurens
Gómez de Liaño, Alfonso
Montesdeoca, Cristina
De Meulenaere, Astrid
Croes, Lieselot
Delombaerde, Danielle
Szabados, Bernadett
Powles, Thomas
First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title_full First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title_fullStr First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title_full_unstemmed First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title_short First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients
title_sort first evidence of activity of enfortumab vedotin on brain metastases in urothelial cancer patients
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057070/
https://www.ncbi.nlm.nih.gov/pubmed/36986475
http://dx.doi.org/10.3390/ph16030375
work_keys_str_mv AT vulstekechristof firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT decockerlaurens firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT gomezdelianoalfonso firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT montesdeocacristina firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT demeulenaereastrid firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT croeslieselot firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT delombaerdedanielle firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT szabadosbernadett firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients
AT powlesthomas firstevidenceofactivityofenfortumabvedotinonbrainmetastasesinurothelialcancerpatients