Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 31 January 2023 / Approved: 1 February 2023 / Online: 1 February 2023 (16:46:24 CET)

A peer-reviewed article of this Preprint also exists.

Vulsteke, C.; De Cocker, L.; Gómez de Liaño, A.; Montesdeoca, C.; De Meulenaere, A.; Croes, L.; Delombaerde, D.; Szabados, B.; Powles, T. First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients. Pharmaceuticals 2023, 16, 375. Vulsteke, C.; De Cocker, L.; Gómez de Liaño, A.; Montesdeoca, C.; De Meulenaere, A.; Croes, L.; Delombaerde, D.; Szabados, B.; Powles, T. First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients. Pharmaceuticals 2023, 16, 375.

Abstract

Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemo-therapy and a PD-1 or PD-L1 inhibitor. The confirmed overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published about the activity in brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old male Caucasian patient, who was 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. The first evaluation after three cycles of EV showed a partial remission by RECIST v1.1 with a near complete response in the brain metastasis and disappear-ance of the neurological complaints. 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 maintenance avelumab. The patient achieved complete response and remained on therapy for five months. However, therapy was discontinued at the patient’s re-quest. 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 male Caucasian patient also received EV, after previous progression on cisplatin-gemcitabine and ate-zolizumab maintenance followed by palliative whole brain radiotherapy and two cycles of vin-flunine. The first evaluation after three cycles of EV showed a significant reduction of the brain metastases. The patient is currently still receiving EV. These are the first reports on efficacy of EV in patients with urothelial carcinoma and active brain metastases.

Keywords

enfortumab vedotin; brain metastases; antibody-drug conjugate

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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