The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma.
Aged
Alopecia
/ chemically induced
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Benzimidazoles
/ administration & dosage
Carbamates
/ administration & dosage
Drug Eruptions
/ etiology
Female
Hand-Foot Syndrome
/ etiology
Humans
Keratosis
/ chemically induced
Male
Melanoma
/ drug therapy
Middle Aged
Mutation
Proto-Oncogene Proteins B-raf
/ genetics
Skin Neoplasms
/ drug therapy
Sulfonamides
/ administration & dosage
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
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.
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
686-692Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 European Academy of Dermatology and Venereology.