Although most dermatologic adverse effects (AEs) of selective fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are mild or moderate, they can be more severe, according to a review published in the Oncologist.1

The FGFR tyrosine kinase family consists of 4 members: FGFR1, -2, -3, and -4. Genomic/transcriptomic alterations associated with these tyrosine kinases, such as point mutations, gene amplifications, gene fusions, and overexpression, can result in oncogenesis through the overactivation of downstream signaling processes, including pathways involving mitogen activated protein kinase (MAPK), and phosphoinositide-3-kinase (PI3K)/Akt.

Nonselective, multikinase inhibitors that also inhibit FGFR, such as ponatinib, have been available for a number of years; therefore, FGFR alterations have been considered actionable in the setting of cancer for some time. However, 2 selective FGFR TKIs were recently granted approval by the US Food and Drug Administration (FDA): Erdafitinib for the treatment of advanced/metastatic urothelial cancer and pemigatinib for the treatment of advanced/metastatic cholangiocarcinoma.2,3 In addition, a number of other selective FGFR TKIs, including derzantinib, infigratinib, rogaratinib, futibatinib, and debio, are in clinical development.


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Specific types of mostly mild/moderate dermatologic AEs, including alopecia, mucositis/stomatitis, dry skin, nail changes, palmar-plantar erythrodysesthesia syndrome (PPES), and calcinosis cutis (a disorder characterized by the deposition of calcium salts in the skin or subcutaneous tissue), have been observed in clinical trials of selective FGFR inhibitors administered to patients with advanced urothelial cancer and advanced cholangiocarcinoma.  In addition, calciphylaxis, a nonuremic condition associated with intimal vascular calcifications and grade 3/4 skin necrosis, was also observed in rare cases. Hence, the main aim of this review was to “increase awareness of skin events and provide effective treatment strategies,” the authors noted.

Regarding the timing of dermatologic AE manifestation, stomatitis and dry mouth were reported as likely to occur within the first 2 weeks of treatment, whereas PPES, nail changes, dry skin, and alopecia were more likely to occur in weeks 2 through 6, 4 through 8, 6 and 7, and 8, respectively, following initiation of selective FGFR TKI therapy. 

Although information regarding effective approaches to prevent most of these dermatologic AEs was limited, the authors emphasized the importance of patient education and early intervention in mitigating their severity. Some management strategies the study authors highlighted included the following:

  • Paronychia Apply topical povidone iodine 2% to 10% or soak the nail in 1:1 solution of vinegar and water for grade 1, and a course of oral antibiotics for grade 2/3
  • Onycholysis Trim the nail and apply topical povidone iodine 2% to 10%; consider oral antibiotics if bacterial infection is suspected
  • Alopecia Topical minoxidil 5% 
  • PPES 10% or higher urea for PPES classified as at least grade 1, with addition of high‐potency topical steroids for grade 2 or higher
  • Grade 1/2 stomatitis Dexamethasone 0.5 mg/5 mL elixir
  • Calcinosis cutis Drug discontinuation with consideration of oral or topical calcium channel blockers, intravenous immunoglobulin, and compounded or intralesional sodium thiosulfate
  • Calciphylaxis Drug discontinuation and 3 times weekly intravenous sodium thiosulfate or intralesional sodium thiosulfate diluted 1:1 with 1% lidocaine every 3 to 4 weeks

“Notably, although treatment for skin toxicities will be initiated by the oncologic team, referral to a dermatologist for consultation is recommended for patients with grade 3/intolerable grade 2 events, or grade 2 events that have not responded to [at least] 4 weeks of therapy,” the authors stated.

References

  1. Lacouture ME, Sibaud V, Anadkat MJ, et al. Dermatologic adverse events associated with selective fibroblast growth factor receptor inhibitors: overview, prevention, and management guidelines. Oncologist. Published online October 5, 2020. doi:10.1002/onco.13552
  2. Balversa [package insert]. Horsham, PA: Janssen Products LP; 2020.
  3. Pemazyre [package insert]. Wilmington, DE: Incyte Corporation; 2020.