Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Asian People
Female
Humans
Japan
/ epidemiology
Male
Melanoma
/ drug therapy
Middle Aged
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Progression-Free Survival
Protein Kinase Inhibitors
/ adverse effects
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
Retrospective Studies
Skin Neoplasms
/ drug therapy
Time Factors
Young Adult
Asian
BRAF inhibitor
Brain metastasis
Melanoma
Prognostic factor
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
20
08
2020
revised:
20
11
2020
accepted:
14
12
2020
pubmed:
28
1
2021
medline:
21
9
2021
entrez:
27
1
2021
Statut:
ppublish
Résumé
As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations. Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed. We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia. B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.
Sections du résumé
BACKGROUND
As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations.
MATERIAL AND METHODS
Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed.
RESULTS
We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia.
CONCLUSION
B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.
Identifiants
pubmed: 33503528
pii: S0959-8049(20)31446-5
doi: 10.1016/j.ejca.2020.12.021
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-220Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.