Management of Nail Toxicities From Fibroblast Growth Factor Receptor Inhibitors

Area of Science:

• Oncology
• Pharmacology
• Dermatology

Background:

• Fibroblast growth factor receptor (FGFR) signaling alterations are implicated in various cancers.
• FGFR inhibitors (FGFRi) are increasingly used for treating urothelial carcinoma, cholangiocarcinoma, and gastrointestinal cancers.
• Nail toxicities (e.g., onycholysis, paronychia) are an underrecognized adverse effect of FGFRi.

Purpose of the Study:

• To systematically review and characterize FGFR inhibitor-associated nail disorders.
• To analyze the incidence, severity, onset, and management of FGFRi-related nail toxicities.
• To identify needs for future research in FGFRi-induced nail complications.

Main Methods:

• Systematic literature review of PubMed and Google up to March 2025.
• Inclusion of case reports, trials, and retrospective studies on FGFRi and nail adverse events.
• Extraction of data on incidence, severity (CTCAE v5.0), onset, management, and treatment impact; statistical analysis using Wilcoxon and Chi-square tests.

Main Results:

• Analysis of 23 studies involving 1,561 patients; 540 experienced nail toxicity.
• Highest nail toxicity rate with erdafitinib (43.3%), lowest with derazantinib (5.3%).
• Grade 1-2 events were most common; Grade 3 events led to dose reduction in 3/540 patients; no treatment discontinuations reported. Management included antiseptic soaks, topical steroids, oral antibiotics, and protective nail care.

Conclusions:

• FGFRi-associated nail toxicities vary by agent, impacting quality of life and treatment adherence.
• Pathogenesis and predictive biomarkers for FGFRi nail toxicity remain unclear.
• Optimized management and preventative strategies require further research; early recognition and multidisciplinary care are essential.