Cutaneous reactions to targeted therapies in children with CNS tumors: A cross‐sectional study

Abstract

Background MAPK (RAS–RAF–MEK–ERK–MAP) and mTOR inhibitors are novel treatments for pediatric central nervous system (CNS) tumors. The literature on common cutaneous adverse reactions to these therapies is sparse in the pediatric population. The aim of this study was to describe common cutaneous adverse reactions to BRAF, MEK, and mTOR inhibitors in children with CNS tumors. Methods In this cross‐sectional study, patients younger than 21 years of age receiving BRAF, MEK, and mTOR inhibitor monotherapy for a CNS tumor were enrolled over a one‐year period. Full body skin examination, photographs of dermatologic findings, and initial treatment recommendations were included at the initial visit, and follow‐up skin examinations were recommended every three months. Results Twenty‐two patients were enrolled in the study. Fifty percent (11/22) received trametinib, a MEK inhibitor, 27.3% (6/22) received dabrafenib, a BRAF inhibitor, and 22.7% (5/22) received everolimus, an mTOR inhibitor. Median age at visit was 11 years (range, 3–19). Median time from treatment initiation to skin examination was 4.5 months (range, 0–43). Ninety‐six percent (21/22) of all patients had at least one skin reaction. The most common reactions across treatment groups included follicular/acneiform eruptions and xerosis. Two patients on MEK inhibitors and one patient on a BRAF inhibitor required therapy cessation due to severe cutaneous reactions. Conclusions Cutaneous reactions to targeted anticancer therapy in children are common, treatable, and rarely require drug dose reduction or discontinuation. Routine surveillance and early intervention may improve quality of life and facilitate continuation of life‐saving therapy.

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

“…The best evidence comes from two studies conducted by pediatric dermatologists evaluating a combined 50 patients receiving BRAF inhibitors. 68,69 Follicular eruptions were most commonly reported, occurring in 55%-100% of patients, and were characterized as KP-like or comedonal and distributed on the extremities and scalp. [68][69][70] Inflammatory papules and pustules were less common (18%), particularly in children younger than 8 (5%).…”

“…68,69 Follicular eruptions were most commonly reported, occurring in 55%-100% of patients, and were characterized as KP-like or comedonal and distributed on the extremities and scalp. [68][69][70] Inflammatory papules and pustules were less common (18%), particularly in children younger than 8 (5%). 68,69 Pruritic xerotic/eczematous dermatitis (36%-50%), photosensitivity (36%), hand-foot skin reaction (HFSR; 36%-83%), and hair changes (alopecia and changes in color or texture; 30%)…”

“…[68][69][70] Inflammatory papules and pustules were less common (18%), particularly in children younger than 8 (5%). 68,69 Pruritic xerotic/eczematous dermatitis (36%-50%), photosensitivity (36%), hand-foot skin reaction (HFSR; 36%-83%), and hair changes (alopecia and changes in color or texture; 30%)…”

Dabrafenib‐induced neutrophilic panniculitis in a child undergoing dual BRAF‐MEK inhibitor therapy for glioblastoma multiforme

“…Our patient was on dual BRAF‐MEK inhibitor therapy with dabrafenib and trametinib when the eruption occurred. Although a single case of suspected MEK inhibitor‐induced panniculitis has been reported in a patient undergoing dual BRAF‐MEK inhibitor therapy, 5 this adverse event is generally thought to be caused by the BRAF inhibitor in such scenarios, as there have been no reported cases of panniculitis while on MEK inhibitor monotherapy 1 . Similar to other reported cases of vemurafenib‐induced panniculitis, our patient's symptoms developed within several weeks of starting dabrafenib with a waxing and waning course 2,3 .…”

Management of skin adverse reactions in oncology

“…67 With respect to pediatric population, doxycycline and minocycline can be prescribed to children older than eight years old and amoxicillin to children younger than eight years old. 68 Erythromycin (macrolide) is not an appropriate first-line choice as oral antibiotics unless the tetracyclines are contraindicated. 69 Treatment with topical antibiotics such as erythromycin and clindamycin 70,71 or the association of clindamycin and benzoyl peroxide 71 can also be a useful therapeutic approach.…”