Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study

Boull, Christina; Gardeen, Samantha; Abdali, Talal; Li, Edward; Potts, Jolee G.; Rubin, Nathan; Carlberg, Valerie M.; Gupta, Deepti; Hunt, Raegan; Luu, Minnelly; Maguiness, Sheilagh; Moertel, Christopher L.; Song, Hannah; Vivar, Karina L.; Coughlin, Carrie C.; Huang, Jennifer T.; Lara‐Corrales, Irene

doi:10.1016/j.jaad.2020.07.044

Cited by 18 publications

(45 citation statements)

References 37 publications

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“…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%).…”

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

“…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%)…”

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

“…[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%)…”

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

“…were also common, occurring in ~ 30%-80% of patients within the first weeks to months of therapy (Figure 4). 68,69,71 It is important to note that these patients are susceptible to ultraviolet radiation A (UVA), which penetrates glass windows, and even minimal exposure (<30 minutes) may result in severe burns. 70 HFSR due to BRAF inhibitors is characterized by hyperkeratosis of the pressure points on the palms and soles.…”

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

“…of patients in Boull's multiinstitutional study, including eruptive nevi (23%), neutrophilic panniculitis (16%), periorbital edema and hyperpigmentation (case reports), delayed wound healing (case reports), and erythema multiforme-like reaction (case reports). 9,11,64,65,69,[72][73][74][75][76][77][78][79][80][81][82][83] While these AEs were mostly characterized as mild (grade 1-2), severe photosensitivity and diffuse morbilliform rash have been reported.…”

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

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Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Carlberg

Davies

Brandling‐Bennett

et al. 2020

Pediatric Dermatology

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The incidence of cancer from birth to 20 years of age is 18.7 per 100 000 and continues to increase. 1 Although mortality has steadily declined, cancer remains one of the leading causes of death from disease in pediatric patients. Targeted anticancer therapies are among the most recently developed agents to address this issue. 2 Key tenets of oncogenesis include uncontrolled cellular growth, tumor metastasis, and evasion of host defenses. 3 Targeted anticancer therapies are small-molecule drugs or monoclonal antibodies that interrupt oncogenesis through a variety of mechanisms (Figure 1). 4 They can act directly on cancer cells to affect cellular proliferation, differentiation, or apoptosis. 3,4 They may also inhibit tumor vasculature, reducing nutrients required for tumor growth or the potential for tumor metastasis. 3,4 Moreover, they may act on immune checkpoint proteins, activating the body's response to cancer. 3,4 This latter mechanism of action is known as targeted immunotherapy. 3-5 As the molecular basis of a specific cancer is uncovered, and particular signaling molecules are found to be upregulated, candidate targeted therapies provide greater specificity than traditional chemotherapy which non-selectively inhibits all rapidly dividing cells. This "precision medicine" has shifted treatment from using medications to target a class of diseases to choosing medications targeting the molecular pathways underpinning disease. Targeted therapies have different side-effect profiles than conventional cytotoxic agents, which were covered in Part I of this two-part series. 6,7 The adverse events (AEs) from targeted therapies may be limited to tissues uniquely targeted by these

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Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

Section: Cellul Ar Targ E Tsmentioning

confidence: 99%

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Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Carlberg

Davies

Brandling‐Bennett

et al. 2020

Pediatric Dermatology

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Outcome Measurement Instruments Used to Evaluate Dermatologic Adverse Events in Cancer Trials

Shaigany,

Mastacouris,

Tannenbaum

et al. 2024

JAMA Dermatol

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ImportanceAssessment of type, severity, and impact of dermatologic adverse events (DAEs) necessitates well-developed and validated clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) that evaluate concepts specific to mucocutaneous toxic effects and that allow appropriate interpretation and comparison of DAEs across trials.ObjectiveTo evaluate heterogeneity and quality of ClinROMs and PROMs used to assess DAEs from systemic cancer therapy.Evidence ReviewTwo systematic reviews were conducted by searching PubMed and Embase databases from inception through March 7, 2023, and April 12, 2023. The first search included randomized clinical trials and observational studies reporting systemic cancer treatment–induced DAEs assessed by a ClinROM or PROM. The second included studies evaluating measurement properties of frequently used ClinROM and PROM instruments. The Consensus-Based Standards for the Selection of Health Measurement Instruments risk of bias tool was used to evaluate methodologic quality of validation assessments.FindingsA total of 395 studies were included. The Common Terminology Criteria for Adverse Events (CTCAE) was utilized in 331 studies meeting inclusion criteria (83.8%). At least 1 skin-related PROM was infrequently utilized in systemic chemotherapy clinical trials (79 studies [20.0%]). Most frequently utilized PROMs were the Dermatology Life Quality Index (DLQI; 34 studies [8.6%]) and Skindex-16 (20 studies [5.1%]). Among studies capturing DAEs, 115 (29.1%) reported a nondescript term (ie, rash) as the only DAE. Eight studies described 44 property assessments of the CTCAE, DLQI, and Skindex. There were no studies evaluating content validity, intrarater reliability, or measurement error for the CTCAE, DLQI, or Skindex. There were no studies evaluating structural validity, internal consistency, and responsiveness of DLQI or Skindex. Interrater reliability and responsiveness were each assessed for 1 DAE-related component of the CTCAE. Construct validity for CTCAE, DLQI, and Skindex was evaluated in 29 (65.9%), 3 (6.8%), and 9 (20.5%) assessments, respectively.Conclusions and RelevanceIn this systematic review, there was a narrow spectrum of ClinROMs and PROMs with limited validity for the measurement of DAEs in the context of systemic chemotherapy interventions in clinical trials. Report of trial DAEs often had low morphologic specificity and meaning. Based on existing gaps in measurement and report of DAEs, a frequent and impactful adverse event to chemotherapy, the framework for evaluating cutaneous toxic effects in oncology trials may need collaborative reevaluation.

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Histopathologic features of selumetinib‐induced paronychia in a child with neurofibromatosis type 1

Borgia,

Ferro,

Piccolo

et al. 2023

JEADV Clinical Practice

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We report a 4‐year‐old girl developing therapy refractory paronychia induced by selumetinib, an oral selective inhibitor of mitogen‐activated protein kinase 1/2 prescribed for a large submandibular plexiform neurofibroma. Although this cutaneous reaction is well‐known and more prevalent in children than in adults, no histopathological characterisations of nail unit toxicity in children on selumetinib have been reported so far. We show histopathological studies on patient‐derived periungual inflamed skin to investigate the cutaneous impact of selumetinib therapy. Our findings are consistent with those of epidermal growth factor receptor inhibitors and support the role of a non‐specific immune activation rather than opportunistic infection in the underlying mechanism of the disease. Partial bilateral matricectomies with electrocautery were resolutive, and the child restarted selumetinib with no recurrence of paronychia during a follow‐up period of 3 months after nail surgery.

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Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study

Cited by 18 publications

References 37 publications

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy

Outcome Measurement Instruments Used to Evaluate Dermatologic Adverse Events in Cancer Trials

Histopathologic features of selumetinib‐induced paronychia in a child with neurofibromatosis type 1

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