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Background <p>Patients with locally advanced or metastatic urothelial carcinoma (mUC) have an unfavorable prognosis, with a&#xa0;5-year survival rate of 12% in women and 14% in men. The antibody–drug conjugate enfortumab vedotin (EV) in combination with the PD‑1 inhibitor pembrolizumab has become standard of care in first-line therapy. Alternatives include the combination of cisplatin, gemcitabine, and nivolumab or chemotherapy with cisplatin or carboplatin and gemcitabine followed by avelumab maintenance therapy if at least stable disease is achieved under chemotherapy.</p> Objective <p>This work aims to present the first-line therapy of mUC in terms of effectiveness and toxicity as well as to provide an outlook of new experimental approaches to first-line treatment.</p> Materials and methods <p>A selective literature review of data from the pivotal studies EV-302, Checkmate-901, and Javelin Bladder is provided, and new therapeutic strategies are discussed.</p> Results <p>First-line treatment with EV and pembrolizumab is applicable for a&#xa0;broad patient population with mUC and is recommended by the guidelines of the European Society for Medical Oncology (ESMO) and the European Association of Urology (EAU). Among cisplatin-eligible patients with contraindications to EV, the combination of nivolumab with gemcitabine and cisplatin constitutes a&#xa0;viable alternative in first line.</p> Conclusion <p>The new therapeutic combinations have significantly changed the treatment standard of mUC since their approval in 2024. The published side effect profiles necessitate multidisciplinary and cross-sectoral management.</p>

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Erstlinienbehandlung des metastasierten Urothelkarzinoms

  • 期刊论文

  • 发表日期：

    2025年11月4日

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  • Stefanie Zschäbitz,
  • Katharina Leucht,
  • Marc-Oliver Grimm,
  • Margitta Retz

摘要

Background

Patients with locally advanced or metastatic urothelial carcinoma (mUC) have an unfavorable prognosis, with a 5-year survival rate of 12% in women and 14% in men. The antibody–drug conjugate enfortumab vedotin (EV) in combination with the PD‑1 inhibitor pembrolizumab has become standard of care in first-line therapy. Alternatives include the combination of cisplatin, gemcitabine, and nivolumab or chemotherapy with cisplatin or carboplatin and gemcitabine followed by avelumab maintenance therapy if at least stable disease is achieved under chemotherapy.

Objective

This work aims to present the first-line therapy of mUC in terms of effectiveness and toxicity as well as to provide an outlook of new experimental approaches to first-line treatment.

Materials and methods

A selective literature review of data from the pivotal studies EV-302, Checkmate-901, and Javelin Bladder is provided, and new therapeutic strategies are discussed.

Results

First-line treatment with EV and pembrolizumab is applicable for a broad patient population with mUC and is recommended by the guidelines of the European Society for Medical Oncology (ESMO) and the European Association of Urology (EAU). Among cisplatin-eligible patients with contraindications to EV, the combination of nivolumab with gemcitabine and cisplatin constitutes a viable alternative in first line.

Conclusion

The new therapeutic combinations have significantly changed the treatment standard of mUC since their approval in 2024. The published side effect profiles necessitate multidisciplinary and cross-sectoral management.