Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines

Abstract

Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example, infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated with tyrosine kinases, the FGFR inhibitors appear to give rise to a number of adverse events affecting the skin. Here we describe these skin events, which include the more common nail adverse events (e.g., onycholysis), palmar-plantar erythrodysesthesia syndrome, and stomatitis, as well as less common reactions such as calciphylaxis. This review aims to provide oncologists with an understanding of these dermatologic events and proposes guidelines for the management of treatment-emergent dermatologic adverse events. Awareness of possible adverse events associated with specific drugs should allow physicians to educate patients as to what to expect and implement effective management plans at the earliest possible opportunity, thereby preventing premature discontinuation while maintaining patient quality of life. The Oncologist 2020;25:1-11 Implications for Practice: Identification of fibroblast growth factor receptor (FGFR) aberrations in cholangiocarcinoma and bladder cancer led to development of selective FGFR inhibitors for these indications, based on clinical benefit and safety profiles. The most frequent adverse events (AEs) include those affecting skin, hair, and nails, a unique class effect of these agents. These are usually mild to moderate in severity. This work reviewed skin AEs reported with FGFR inhibitors and provides management guidelines for physicians, aiming to increase awareness of skin events and provide effective treatment strategies. Early intervention and effective management may improve treatment adherence, optimize outcomes, and improve quality of life.

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

“…A number of pan-FGFR (eg, erdafitinib) and selective FGFR1-3 (eg, infigratinib) or FGFR4 (eg, fisogatinib) agents have been tested in clinical trials for cholangiocarcinoma, bladder cancer, and other solid tumors, with several others currently in the pipeline. 154 The dermatologic toxicities for pan-and selective FGFR inhibitors have been recently reviewed, 155 and are listed in Table 1. [156][157][158] Altered calcium-phosphate homeostasis resulting in hyperphosphatemia is a frequent adverse event from FGFR inhibitors and hyperphosphatemia occurs in 45% to 100% of patients treated with pan-FGFR and FGFR1-3 inhibitors.…”

Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review

“…Dermatological problems, such as dry skin and mucous membranes, nail plate disorder, alopecia and hand–foot syndrome, have been reported during the use of infigratinib in oncology, but we do not know if such effects will occur when using doses of this drug for the treatment of ACH [ 69 ].…”

Quality of Life and Symptom Management in Advanced Biliary Tract Cancers

“…All patients should be educated on anticipated dermatologic toxicities and preventative strategies when starting therapy. Some important preventative strategies include good oral hygiene, regular dentist visits, and use of topical emollients, as well as avoidance of prolonged contact with water, repeated trauma, and pressure [79]. Patients should also be instructed to seek medical evaluation for onycholysis and stomatitis to rule out concomitant infection.…”

“…Patients should also be instructed to seek medical evaluation for onycholysis and stomatitis to rule out concomitant infection. In grade 3 or greater dermatologic toxicities that do not improve with standard topical treatments, early dermatology referral is warranted, and an FGFR inhibitor should be withheld [79]. Once symptoms improve to grade 1 or less, the drug can be restarted at a lower dose.…”