MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis.
Binimetinib
Chemo-resistance
Low grade ovarian cancer
MEK inhibitors
Selumetinib
Trametinib
Journal
Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
13
06
2022
revised:
13
08
2022
accepted:
14
08
2022
pubmed:
6
9
2022
medline:
18
10
2022
entrez:
5
9
2022
Statut:
ppublish
Résumé
Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status. In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis. A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.
Sections du résumé
BACKGROUND
BACKGROUND
Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status.
METHODS
METHODS
In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis.
RESULTS
RESULTS
A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I
CONCLUSIONS
CONCLUSIONS
Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.
Identifiants
pubmed: 36063572
pii: S0305-7372(22)00127-X
doi: 10.1016/j.ctrv.2022.102458
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Types de publication
Journal Article
Meta-Analysis
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
102458Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest 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 paper.