MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis

Cancer Treat Rev. 2022 Nov:110:102458. doi: 10.1016/j.ctrv.2022.102458. Epub 2022 Aug 24.

Abstract

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: 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: 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 (I2 = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 - 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I2 = 85 %; P = 0.009).

Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.

Keywords: Binimetinib; Chemo-resistance; Low grade ovarian cancer; MEK inhibitors; Selumetinib; Trametinib.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Female
  • Humans
  • Mitogen-Activated Protein Kinase Kinases
  • Ovary*
  • Peritoneal Neoplasms* / drug therapy
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases