Alopecia in patients treated with molecularly targeted anticancer therapies

Belum, Viswanath Reddy; Marulanda, Kathleen; Ensslin, Courtney J.; Gorcey, Loren; Parikh, Tapan; Wu, S.; Busam, Klaus J.; Gerber, Peter Arne; Lacouture, Mario E.

doi:10.1093/annonc/mdv390

Cited by 56 publications

(46 citation statements)

References 57 publications

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“…Although we observed alopecia and paronychia only in trametinib patients, these reactions have been observed in patients on both BRAF and mTOR inhibitors in other studies. [17][18][19] Although these reactions can significantly impact quality of life, 20 Our findings must be interpreted in the context of the study design.…”

Section: Discussionmentioning

confidence: 89%

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

Song

Zhong

Kieran

et al. 2019

Pediatric Blood & Cancer

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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.

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Section: Discussionmentioning

confidence: 89%

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

Song

Zhong

Kieran

et al. 2019

Pediatric Blood & Cancer

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“…In targeted therapy, a meta-analysis revealed overall incidence rates of 15% with the highest incidence for the hedgehog inhibitor vismodegib (57%) which often leads to complete hair loss. However, the risk of alopecia is lower than in chemotherapy [20]. …”

Section: Alopeciamentioning

confidence: 99%

Prophylaxis and Management of Skin Toxicities

2019

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Skin toxicity is a common problem not only when treating breast cancer but in all cancer types. Visible on the surface, these side effects come not just with burdening symptoms but also with stigmatization. With increasing diversity in therapeutic options, dermatologic side effects are also becoming increasingly complex and more challenging for the clinician. We reviewed the most common dermatologic side effects of current anticancer therapy, including toxicity induced by chemotherapy, targeted therapy, and immunotherapy. In particular, we focus on xerosis and pruritus, (acneiform) exanthema, hand-foot syndrome, nail toxicities, alopecia, and mucositis. We propose measures for the prevention and management of these side effects based on current literature. With high incidences in both chemotherapy and targeted therapy, prophylactic measures are crucial to reducing the incidence and severity of skin toxicity and therefore key to therapy adherence. Appropriate management of these toxicities will help avoid unnecessary treatment discontinuation.

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“…1 Vismodegib was reported as having the highest overall incidence of all-grade alopecia compared to the other treatments (56.9% of patients) in a recent meta-analysis. 6 Although alopecia is persistent during therapy and can be distressing for patients, it is usually reversible after treatment cessation. 7 The pathomechanism of Hedgehog inhibitor-induced alopecia is very distinct.…”

Section: Funding Sourcesmentioning

confidence: 99%

“…It has been reported that about 58–64% of patients receiving Hedgehog inhibitor treatment for aBCC develop severe hair loss (>50% of the scalp area) . Vismodegib was reported as having the highest overall incidence of all‐grade alopecia compared to the other treatments (56.9% of patients) in a recent meta‐analysis . Although alopecia is persistent during therapy and can be distressing for patients, it is usually reversible after treatment cessation .…”

mentioning

confidence: 99%

Can hair re‐growth be considered an early clinical marker of treatment resistance to Hedgehog inhibitors in patients with advanced basal cell carcinoma? A report of two cases

Soura

Plaka

Dessinioti

et al. 2016

Acad Dermatol Venereol

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Although alopecia is a well-known adverse event associated with the administration of Hh inhibitors, data associated with the appearance and/or clinical severity of alopecia and the treatment efficacy of Hedgehog inhibitors are limited. The Hedgehog pathway plays an important role in the normal cycling of the hair follicles in adults and, therefore, the pathomechanism of Hedgehog inhibitor-induced alopecia is considered unique for this drug class. Based on the fact that Hh inhibitor resistance is associated with partial reactivation of the Hh pathway, it would not be illogical to suggest that reversal of Hh inhibitor-induced alopecia in patients under treatment with Hh inhibitors could serve as a clinical marker of drug resistance. However, this observation, as reported in this paper, is only limited in two patients and therefore more information is needed in order to assess its actual clinical importance.

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Alopecia in patients treated with molecularly targeted anticancer therapies

Cited by 56 publications

References 57 publications

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

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

Prophylaxis and Management of Skin Toxicities

Can hair re‐growth be considered an early clinical marker of treatment resistance to Hedgehog inhibitors in patients with advanced basal cell carcinoma? A report of two cases

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