scholarly journals Targeting the Fibroblast Growth Factor Receptor (FGFR) in Advanced Cholangiocarcinoma: Clinical Trial Progress and Future Considerations

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1706
Author(s):  
Patrick C. Lee ◽  
Andrew Hendifar ◽  
Arsen Osipov ◽  
May Cho ◽  
Daneng Li ◽  
...  

Landmark molecular profiling efforts have identified multiple targetable alterations in cholangiocarcinoma. Among the molecular-driven subsets of cholangiocarcinoma, targeting the fibroblast growth factor receptor (FGFR) has shown promise and represents the first targeted therapy to be approved in treatment-refractory, advanced cholangiocarcinoma. In this review, we provide an up-to-date overview of the clinical development of FGFR inhibitors in advanced cholangiocarcinoma. We review the FGFR pathway and discuss emerging issues including resistance to FGFR inhibitors. We end with a discussion on future considerations to optimize the potential of this class of therapeutics in advanced cholangiocarcinoma.

2019 ◽  
Author(s):  
Eunhae Shin ◽  
Dong Hui Lim ◽  
Jisang Han ◽  
Do-Hyun Nam ◽  
Keunchil Park ◽  
...  

Abstract Background To describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials Retrospective chart review. Results Among 6,871 patients and 17 EGFR or FGFR inhibitors, 1,161 patients (16.9%) referred for ophthalmologic examination. Authors identified that in twelve patients, 3 EGFR inhibitors and 2 FGFR inhibitors that caused corneal epithelial lesions. Vandetanib, Osimertinib, and an EGFR agent under clinical trial (ABT-414) caused vortex keratopathy in nine patients and ASP5878 and FPA144, the FGFR inhibitors of clinical trial caused epithelial changes resembling corneal dysmaturation in three patients. Mean interval until symptoms appear was 246 days with Vandetanib, 196 days with Osimertinib, 30 days with ABT-414, 55 days with ASP5878 and 70 days with FPA144. Mean of lowest logarithm of minimal angle of resolution units (logMAR) visual acuity of right eye after chemotherapy was 0.338 and 0.413 in left eye. Incidence of epithelial changes were 15.79% with Vandetanib, 0.005% with Osimertinib, 100% with ABT414, 50.0% with ASP5878 and 18.2% with FPA144. After excluding deceased patients, or were lost to follow-up or were still undergoing treatment, we confirmed the reversibility of corneal lesions after discontinuation of each agent. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions EGFR and FGFR inhibitors are well known chemotherapy agents and could make corneal epithelial changes. Contrary to low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with EGFR or FGFR inhibitors that decreased visual acuity could develop due to corneal epithelial changes, and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.


2019 ◽  
Author(s):  
Eunhae Shin ◽  
Dong Hui Lim ◽  
Jisang Han ◽  
Do-Hyun Nam ◽  
Keunchil Park ◽  
...  

Abstract Background To describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials Retrospective chart review. Results Among 6,871 patients and 17 EGFR or FGFR inhibitors, authors identified five EGFR inhibitors and two FGFR inhibitors that cause such corneal lesions. Unlike other old EGFR agents with rare ocular complications, Vandetanib, Osimertinib, and 3 EGFR agents under clinical trial (ABT-414, ASP5878, FPA144) caused vortex keratopathy in nine patients and ASP5878 and FPA144, the FGFR inhibitors of clinical trial caused epithelial changes resembling corneal dysmaturation in three patients. ABT-414 showed a remarkably short interval from the start of therapy to initiation of keratopathy. After excluding deceased patients, or were lost to follow-up or were still undergoing treatment, we confirmed the reversibility of corneal lesions after discontinuation of each agent. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions EGFR and FGFR inhibitors are well known chemotherapy agents and could make corneal epithelial changes. Contrary to low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with EGFR or FGFR inhibitors that decreased visual acuity could develop due to corneal epithelial changes, and also reassure them that the condition is reversible after the end of treatment without the use of steroid eye drops.


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