Biomarker-Oriented Therapy in Bladder and Renal Cancer.

Mathijs P Scholtes,Paul C M S Verhagen,Arnout R Alberts,Tahlita C M Zuiverloon,Iris G Iflé,Astrid A M Van Der Veldt

doi:10.3390/ijms22062832

Mathijs P Scholtes, Paul C M S Verhagen + Show 4 more

Open Access

https://doi.org/10.3390/ijms22062832

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Abstract

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor—tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.

Highlights

Bladder cancer and renal cancer are among the 10 most common cancers worldwide.In recent years, significant progress was made in terms of biomarker-oriented treatment for both urogenital cancer types
Axitinib over sunitinib was observed in patients with programmed death-ligand 1 (PD-L1) expression. These studies led to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval of these three treatment combinations in treatment-naïve metastatic renal cell carcinoma (RCC), regardless of PD-L1 expression status, as well as inclusion as first-line treatment in the updated European Association of Urology (EAU) guidelines [75]: for patients in all IMDC risk-groups in case of pembrolizumab + axitinib and avelumab + axitinib), but limited to intermediate and poor-risk disease in case of nivolumab + ipilimumab
The landscape of targeted therapy has changed in recent years for both bladder cancer (BC) and RCC, mainly due to the upcoming of immune checkpoint inhibitors

Summary

Introduction

Bladder cancer and renal cancer are among the 10 most common cancers worldwide. In recent years, significant progress was made in terms of biomarker-oriented treatment for both urogenital cancer types. We provide a comprehensive overview of new developments in targeted therapy for urothelial carcinoma of the bladder and renal carcinoma

Bladder Cancer

Renal Cancer

Clinical Trial Results

10. Second-Line Treatment

11. Novel Second-Line Treatment in VEGFR-TKI-Resistant Disease

13. Conclusions