MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis. (November 2022)

• Record Type: Journal Article
• Authors: Musacchio, Lucia; Valsecchi, Anna Amela; Salutari, Vanda; Valabrega, Giorgio; Camarda, Floriana; Tuninetti, Valentina; Giannone, Gaia; Bartoletti, Michele; Marchetti, Claudia; Pignata, Sandro; Fagotti, Anna; Scambia, Giovanni; Di Maio, Massimo; Lorusso, Domenica
• Is Part Of: Cancer treatment reviews. Volume 110(2022)
• Publication Date: 2022-11
• Subjects: Low grade ovarian cancer -- MEK inhibitors -- Chemo-resistance -- Trametinib -- Binimetinib -- Selumetinib; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2022.102458
• Languages: English
• ISSNs: 0305-7372

Abstract

Highlights: Low grade ovarian cancer is a complex disease characterized by MAPK alterations. MEK inhibitors showed meaningful activity in RAS/RAF mutated patients. Phase II/III trials demonstrated improvement in PFS in low grade ovarian cancer patients. 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 (I 2 = 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 (I 2 = 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.