EP246/#636 The efficacy of mek inhibitors (MEKI) in the treatment of low-grade serous ovarian cancer (LGSC): a systematic review

Objectives

Low response rates of LGSC to traditional systemic therapies prompts the need for novel therapies. LGSC have a high frequency of mutations in the MAPK cascade, which is targeted by MEKi. The primary objective of this systematic review was to assess the overall response rate (ORR) of LGSC to MEKi.

Methods

Pubmed, EMBASE, Medline and the Cochrane Database were searched from inception to March 2022. Inclusion criteria were studies assessing the treatment of LGSC with a MEKi in the primary or recurrent setting, published in English. Case reports, case series, conference proceedings, in vitro studies and animal studies were excluded. Studies were screened and assessed for eligibility by two independent reviewers (AK, CC), with conflicts resolved by a third reviewer (TZ). Data was extracted using pre-established criteria.

Results

Initial literature search identified 1815 papers; four met eligibility criteria. Three were randomized clinical trials and one was a phase II single-arm prospective cohort study. A total of 680 patients were included, of which 416 were treated with a MEKi alone. All patients were treated for recurrent LGSOC. ORR ranged from 12.1 to 26% and median progression-free survival (PFS) ranged from 7.2 to 13 months.

Conclusions

While one study demonstrated significantly improved efficacy of MEKi over physician-choice systemic therapy, another did not show benefit. Two additional studies did not compare MEKi to traditional therapies, limiting their clinical relevance. LGSC with BRAF and KRAF mutations have higher ORR to MEKi. Further prospective and randomized trials are needed to determine the efficacy of MEKi in treating LGSC.