MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature (4 essais incluant un total de 648 patients), cette méta-analyse évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, de différents inhibiteurs de MEK en monothérapie, chez des patients atteints d'un carcinome séreux de bas grade de l'ovaire ou du péritoine
Background : Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized bylow response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinicaltrials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity a nd 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 conferenceproceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independentlyby 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-treatpopulation, use of a MEK inhibitor was not associated with a significant improvementin PFS, with a pooled Hazard Ratio equal to 0.75 (95% CI: 0.30 – 1.86, P=0.54). Heterogeneitywas significant (I2= 92%; P= 0.0004). In the overall study population, the pooled odds ratio of ORR forMEKis 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 availabledata show clear signals of activity, at least for some MEKis.