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Frequency of next-generation sequencing, prevalence of targetable mutations and response to targeted therapies amongst patients with metastatic urothelial cancer in Ireland: a multi-centre retrospective study of real-world data

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Abstract

Background

The genomic knowledge on urothelial carcinoma is expanding. It is recognised that urothelial carcinoma is a disease with a high somatic mutation rate and a high prevalence of genetic alterations, as discussed by Thomas and Sonpavde (2022). In the context of a disease rich with somatic alterations, continuing efforts to better identify which patients may benefit most from targeted therapy, immunotherapy and combination therapy may ultimately lead to improved outcomes for patients with this disease.

Aims

We aimed to ascertain the frequency of next-generation sequencing (NGS) and the prevalence of genomic alterations amongst patients with metastatic urothelial cancer (mUC) in Ireland. We studied patients who received a targeted therapy following the detection of an oncogenic alteration on NGS and assessed their outcomes.

Methods

Patients with a diagnosis of mUC between 2017 and 2022 were identified from Urology MDT databases as well as pharmacy databases across three Irish cancer centres. A retrospective review of patient notes including a comprehensive review of histopathology, radiology data, prior therapies and NGS reports was carried out for each patient.

Results

111 patients diagnosed with mUC between 2017 and 2022 were identified for inclusion across three hospital sites. NGS was carried out on the tumour specimens of 66 patients (59%). Thirty-six potentially therapeutically targetable alterations were identified amongst thirty-five patients. The most frequent alterations identified were PIK3CA mutations, FGFR3 mutations or fusions and ERBB2 somatic mutations. Fifteen patients (13.5%) received therapy directed at a genetic alteration. The most common targeted therapy received was erdafitinib (60%) followed by trastuzumab (33%) with one patient receiving alpelisib monotherapy. The median duration of treatment with targeted therapy was 3 months (range 1–34 months). Two patients were observed to have durable responses to erdafitinib approaching 3 years duration.

Conclusions

This study provides an understanding of the use of NGS and prevalence of genomic alterations in an Irish patient population.

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Data availability

The data that support the findings of this study are available from the corresponding author, KR, upon reasonable request.

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital Waterford, Waterford, Ireland

    Karine Ronan & Emmet Jordan

  2. Department of Medical Oncology, Tallaght University Hospital, Dublin, Ireland

    Christine Leonard

  3. Department of Medical Oncology, St Vincent’s University Hospital; Tallaght University Hospital, Dublin, Ireland

    Ray McDermott

Authors
  1. Karine Ronan
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  2. Emmet Jordan
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  3. Christine Leonard
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  4. Ray McDermott
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Correspondence to Karine Ronan.

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This study was granted approval by the Research Ethics Committee HSE South Eastern Area. This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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The authors declare no competing interests.

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Ronan, K., Jordan, E., Leonard, C. et al. Frequency of next-generation sequencing, prevalence of targetable mutations and response to targeted therapies amongst patients with metastatic urothelial cancer in Ireland: a multi-centre retrospective study of real-world data. Ir J Med Sci 193, 1155–1161 (2024). https://doi.org/10.1007/s11845-023-03569-2

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  • DOI: https://doi.org/10.1007/s11845-023-03569-2

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