Checkpoint Inhibitors in Urothelial Carcinoma—Future Directions and Biomarker Selection

Joshua J. Meeks, Peter C. Black, Matthew Galsky, Petros Grivas, Noah M. Hahn, Syed A. Hussain, Matthew I. Milowsky, Gary D. Steinberg, Robert S. Svatek, Jonathan E. Rosenberg

Producción científica: Review articlerevisión exhaustiva

13 Citas (Scopus)

Resumen

Context: Several recent phase 2 and 3 trials have evaluated the efficacy and toxicity of checkpoint inhibitor (CPI) therapy for urothelial carcinoma (UC) in the metastatic, localized muscle-invasive UC (MIUC), upper tract UC, and non–muscle-invasive bladder cancer (NMIBC) disease state. Objective: To assess the outcomes and toxicity of CPIs across the treatment landscape of UC and contextualize their application to current real-world treatment. Evidence acquisition: We queried PubMed, Web of Science, and EMBASE databases and conference abstracts to identify prospective trials examining CPIs in UC. The primary endpoints included overall survival, recurrence-free survival, and toxicity (when available). A secondary analysis included biomarker evaluation of response. Evidence synthesis: We identified 21 trials, 12 phase 2 and nine phase 3 trials, in which a CPI was used for metastatic UC (seven), MIUC (nine), and NMIBC (five). For first-line (1L) metastatic UC, concurrent chemotherapy with CPIs failed to show superiority. Improved overall and progression-free survival for switch maintenance avelumab (after achieving stable disease or response with induction systemic chemotherapy) has established the current standard of care for 1L metastatic UC. A single-agent CPI is a consideration for patients unable to tolerate chemotherapy. CPIs in the perioperative setting are limited to only the adjuvant treatment with nivolumab after radical surgery for MIUC in patients at a higher risk of recurrence based on pathologic stage. Only pembrolizumab is approved by the Food and Drug Administration for carcinoma in situ unresponsive to bacillus Calmette-Guérin (BCG) in patients who are not fit for or who refuse radical cystectomy. Trials investigating CPIs in combination with multiple immune regulators, antibody drug conjugates, targeted therapies, antiangiogenic agents, chemotherapy, and radiotherapy are enrolling patients and may shape the future treatment of patients with UC. Conclusions: CPIs have an established role across multiple states of UC, with broadened applications likely to occur in the future. Several combinations are being evaluated, while the development of predictive biomarkers and their validation may help identify patients who are most likely to respond. Patient summary: Our findings highlight the broad activity of checkpoint inhibitors in urothelial carcinoma, noting the need for further investigation for the best application of combinations and patient selection to patient care.

Idioma originalEnglish (US)
Páginas (desde-hasta)473-483
Número de páginas11
PublicaciónEuropean Urology
Volumen84
N.º5
DOI
EstadoPublished - nov 2023

ASJC Scopus subject areas

  • Urology

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