scholarly journals FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2968
Author(s):  
Anuhya Kommalapati ◽  
Sri Harsha Tella ◽  
Mitesh Borad ◽  
Milind Javle ◽  
Amit Mahipal
Keyword(s):  
Clinical Utility ◽  
Fibroblast Growth Factor Receptor ◽  
Treatment Guidelines ◽  
Growth Factor Receptor ◽  
The United States ◽  
Resistance Mechanisms ◽  
Effective Management ◽  
Metastatic Urothelial Carcinoma ◽  
Accelerated Approval ◽  
Inhibitor Resistance

Fibroblast Growth Factor receptor (FGFR) pathway aberrations have been implicated in approximately 7% of the malignancies. As our knowledge of FGFR aberrations in cancer continues to evolve, FGFR inhibitors emerged as potential targeted therapeutic agents. The promising results of pemigatinib and infigratinib in advanced unresectable cholangiocarcinoma harboring FGFR2 fusions or rearrangement, and erdafitinib in metastatic urothelial carcinoma with FGFR2 and FGFR3 genetic aberrations, lead to their accelerated approval by the United States (USA) FDA. Along with these agents, many phase II/III clinical trials are currently evaluating the use of derazantinib, infigratinib, and futibatinib either alone or in combination with immunotherapy. Despite the encouraging results seen with FGFR inhibitors, resistance mechanisms and side effect profile may limit their clinical utility. A better understanding of the unique FGFR-inhibitor-related toxicities would invariably help us in the prevention and effective management of FGFR-inhibitor-induced adverse events thereby enhancing their clinical benefit. Herein, we summarized the physiology of FGF/FGFR signaling and briefly discussed the possible mechanisms that could lead to FGFR inhibitor resistance and side effects. In addition, we proposed treatment guidelines for the management of FGFR-inhibitor-associated toxicities. This work would invariably help practicing oncologists to effectively manage the unique toxicities of FGFR inhibitors.

Fibroblast Growth Factor Receptor Inhibitor–Associated Multifocal Serous Retinal Detachments: A Case Report

2021 ◽  
pp. 247412642110136
Author(s):  
Diana H. Kim ◽  
Tian Xia ◽  
Peter Bracha ◽  
Brian L. VanderBeek
Keyword(s):  
Case Report ◽  
Growth Factor ◽  
Urothelial Carcinoma ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Metastatic Urothelial Carcinoma ◽  
Optical Coherence Tomography Imaging ◽  
Receptor Inhibitor

Purpose: This report aims to describe a case of bilateral, multifocal neurosensory retinal detachments that developed during erdafitinib therapy for metastatic urothelial carcinoma. Methods: A case report with color fundus imaging and spectral-domain optical coherence tomography imaging is presented. Results: A 50-year-old man with metastatic urothelial carcinoma had an unremarkable baseline ophthalmic examination prior to starting erdafitinib. At 3-month follow up, an examination revealed bilateral, multifocal retinal detachments. Because the patient was asymptomatic and erdafitinib was the only drug to which his tumor had responded, he was kept on the medication with close ophthalmic monitoring. Conclusions: Erdafitinib, a fibroblast growth factor receptor inhibitor, can cause bilateral, multifocal retinal detachments. Continuation of erdafitinib may be considered in patients without significant visual impairment when the overall benefit of the medication appears to outweigh the risks.

MSK-ACCESS for the detection of fibroblast growth factor receptor-3 (FGFR3) mutations in plasma cell-free (cf)DNA of metastatic urothelial carcinoma (mUC) patients (pts) pre- and on erdafitinib (erda) therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17034-e17034
Author(s):  
Michal Sarfaty ◽  
Min Yuen Teo ◽  
Samuel Aaron Funt ◽  
Chung-Han Lee ◽  
David Henry Aggen ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Mutant Allele ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Plasma Samples ◽  
Fgfr3 Mutation ◽  
Metastatic Urothelial Carcinoma ◽  
Pre Treatment ◽  
High Degree ◽  
Fgfr3 Mutations

e17034 Background: The pan-FGFR inhibitor erda was recently FDA-approved for pretreated mUC pts harboring FGFR2/3 alterations. We explored concordance of FGFR3 mutation profiles between the primary tumor and cfDNA using the MSK-ACCESS platform. We also correlated changes in FGFR3 cfDNA mutant allele fraction (MAF) with response to drug. Methods: Plasma samples were collected from mUC pts started on erda at baseline, on treatment (tx), and at progression. Demographic and clinical characteristics were obtained. Baseline tumors were sequenced with MSK-IMPACT (ref) and plasma samples were sequenced using MSK-ACCESS, a cfDNA platform that sequences 129 genes using unique molecular indexes to generate > 15,000x coverage and detection of somatic mutations down to 0.1% MAF. Results: Between 08/2019-1/2020, 11 pts received erda 8mg daily. Of these, 3 pts increased dose to 9mg daily based on phosphorus level, 4 required dose reductions and 6 dose interruptions. In 5 pts, erda was discontinued for disease progression. FGFR3 S249C was the most frequent alteration detected (64%) followed by Y373C (18%), R248C and S371C (both 9%). Pre-treatment plasma FGFR3 profiles were concordant with tissue in 91% (10/11) of pts and additional FGFR3 mutations were detected in 3 cases (27%, Table), including 1 pt with an FGFR3-TACC3 fusion and hotspot mutations only in cfDNA. In 2 responding pts, the mutant allele was undetectable on erda. Conclusions: A high degree of concordance between primary tumor and cfDNA FGFR3 mutation detection was observed. FGFR3 mutations exclusive to cfDNA were found in a subset of pts. Further pt accrual and follow-up are ongoing to assess for correlations between erda response and tx-related changes in cfDNA MAF, and to assess whether cfDNA can identify resistance mechanisms. [Table: see text]

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