The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma.


Journal

Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037

Informations de publication

Date de publication:
Apr 2019
Historique:
received: 18 03 2018
accepted: 23 10 2018
pubmed: 24 11 2018
medline: 6 8 2019
entrez: 24 11 2018
Statut: ppublish

Résumé

B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib). The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib. Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%). Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.

Sections du résumé

BACKGROUND BACKGROUND
B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib).
OBJECTIVE OBJECTIVE
The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib.
METHODS METHODS
Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature.
RESULTS RESULTS
The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%).
CONCLUSION CONCLUSIONS
Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.

Identifiants

pubmed: 30468696
doi: 10.1111/jdv.15363
doi:

Substances chimiques

Benzimidazoles 0
Carbamates 0
Sulfonamides 0
binimetinib 181R97MR71
encorafenib 8L7891MRB6
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Pagination

686-692

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2018 European Academy of Dermatology and Venereology.

Auteurs

N P Graf (NP)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

P Koelblinger (P)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.

N Galliker (N)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

S Conrad (S)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

M Barysch (M)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

J Mangana (J)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

R Dummer (R)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

P F Cheng (PF)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

S M Goldinger (SM)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

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Classifications MeSH