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Review
. 2022 Sep 27:16:11795549221126252.
doi: 10.1177/11795549221126252. eCollection 2022.

Immunotherapy With Checkpoint Inhibitors in FGFR-Altered Urothelial Carcinoma

David J Benjamin  1 , Nataliya Mar  2 , Arash Rezazadeh Kalebasty  2
Affiliations
Review

Immunotherapy With Checkpoint Inhibitors in FGFR-Altered Urothelial Carcinoma

David J Benjamin et al. Clin Med Insights Oncol. .

Abstract

The treatment landscape of metastatic urothelial cancer (mUC) remained unchanged for over 30 years until the approval of immune checkpoint inhibitors (ICIs) in 2016. Since then, several ICIs have been approved for the treatment of mUC. In addition, recent molecular characterization of bladder cancer has revealed several subtypes, including those harboring fibroblast growth factor receptor (FGFR) mutations and fusion proteins. Erdafitinib, a pan-FGFR inhibitor, was approved for the treatment of metastatic/advanced UC in 2019. Some available evidence suggests ICI may have inferior response in advanced FGFR+ UC for unclear reasons, but may possibly be related to the tumor microenvironment. Several ongoing trials are evaluating erdafitinib in metastatic/advanced UC including the ongoing phase IB/II NORSE trial combining erdafitinib plus ICI, which may prove to offer a more robust and durable response in patients with FGFR+ metastatic/advanced UC.

Keywords: FGFR; Urothelial carcinoma; bladder cancer; checkpoint inhibitor; erdafitinib; immunotherapy.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Nataliya Mar. Speakers’ Bureau: Seattle Genetics. Arash Rezazadeh Kalebasty. Stock and Other Ownership Interests: ECOM Medical; Consulting or Advisory Role: Exelixis, AstraZeneca, Bayer, Pfizer, Novartis, Genentech, Bristol Myers Squibb, EMD Serono, Immunomedics, and Gilead Sciences; Speakers’ Bureau: Janssen, Astellas Medivation, Pfizer, Novartis, Sanofi, Genentech/Roche, Eisai, AstraZeneca, Bristol Myers Squibb, Amgen, Exelixis, EMD Serono, Merck, Seattle Genetics/Astellas, Myovant Sciences, Gilead Sciences, and AVEO; Research Funding: Genentech, Exelixis, Janssen, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Macrogenics, Astellas Pharma, BeyondSpring Pharmaceuticals, BioClin Therapeutics, Clovis Oncology, Bavarian Nordic, Seattle Genetics, Immunomedics, and Epizyme; Travel, Accommodations, Expenses: Genentech, Prometheus, Astellas Medivation, Janssen, Eisai, Bayer, Pfizer, Novartis, Exelixis, and AstraZeneca.

Figures

Figure 1.
Figure 1.
FGF/FGFR signaling pathway. AKT indicates Ak strain transforming; FGFR, fibroblast growth factor receptor; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase. Source: Adapted from BioRender.com. License permits BioRender content to be sublicensed for use in Clinical Medicine Insights: Oncology.
Figure 2.
Figure 2.
Immunomodulatory effect of erdafitinib. Source: Adapted from BioRender.com. License permits BioRender content to be sublicensed for use in Clinical Medicine Insights: Oncology.
See this image and copyright information in PMC

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