INTRODUCTION
Fibroblast growth factor receptor inhibitors (FGFRi) are a novel class of targeted therapies used in the treatment of FGFR-mutant malignancies. Aberrant FGFR signaling via gene amplification, overexpression, activating mutations, or gene fusions is implicated in a variety of cancers, including breast, gynecological, urothelial, hematopoietic, and gastrointestinal malignancies.1 In this study, we focused on the current FDA-approved selective FGFRi which include pemigatinib, futibatinib, and erdafitinib along with new FGFRi that are currently under clinical trials.2,3
While dermatologic toxicities such as acneiform dermatitis, xerosis, and mucositis are well-recognized adverse effects of many targeted oncologic therapies, FGFRi have a unique propensity to cause nail toxicities that may be less familiar to the oncologist or general dermatologist. FGFR signaling is important for cellular homeostasis of the nail unit, and blocking this pathway can lead to nail dystrophy, fragility, detachment, or inflammation.4 While FGFR1 and FGFR2 primarily regulate epithelial and mesenchymal tissues such as skin and nails, direct evidence linking nail toxicities to inhibition of specific FGFR complexes remains limited.
There remains a lack of comprehensive literature focused specifically on the clinical characteristics, incidence, and management of FGFR inhibitor-related nail toxicities. Most available data on FGFRi-associated nail disorders are limited to isolated case reports or brief mentions within broader studies of cutaneous adverse events of these drugs. This has led to underrecognition of these findings in both clinical practice and clinical trial reporting. Given the growing use of FGFRi across multiple malignancies and the role nail disorders can play in negatively impacting patient quality of life, there is a clear need for a consolidated review of current knowledge. Therefore, we conducted this systematic review to compile and analyze all available evidence on FGFRi-associated nail toxicity, to improve recognition, facilitate earlier intervention, and guide future research efforts in this area.
While dermatologic toxicities such as acneiform dermatitis, xerosis, and mucositis are well-recognized adverse effects of many targeted oncologic therapies, FGFRi have a unique propensity to cause nail toxicities that may be less familiar to the oncologist or general dermatologist. FGFR signaling is important for cellular homeostasis of the nail unit, and blocking this pathway can lead to nail dystrophy, fragility, detachment, or inflammation.4 While FGFR1 and FGFR2 primarily regulate epithelial and mesenchymal tissues such as skin and nails, direct evidence linking nail toxicities to inhibition of specific FGFR complexes remains limited.
There remains a lack of comprehensive literature focused specifically on the clinical characteristics, incidence, and management of FGFR inhibitor-related nail toxicities. Most available data on FGFRi-associated nail disorders are limited to isolated case reports or brief mentions within broader studies of cutaneous adverse events of these drugs. This has led to underrecognition of these findings in both clinical practice and clinical trial reporting. Given the growing use of FGFRi across multiple malignancies and the role nail disorders can play in negatively impacting patient quality of life, there is a clear need for a consolidated review of current knowledge. Therefore, we conducted this systematic review to compile and analyze all available evidence on FGFRi-associated nail toxicity, to improve recognition, facilitate earlier intervention, and guide future research efforts in this area.
MATERIALS AND METHODS
A systematic literature search was conducted using PubMed and Google. Keywords included "FGFR inhibitor," along with the individual medications under this class, including erdafitinib, pemigatinib, futibatinib, infigratinib, and derazantinib. Specific terms for nail toxicities used in the search included nail, nail changes, onycholysis, brittle nails, onychodystrophy, Beau's
