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The MEK inhibitor trametinib more than doubled the time to progression compared with chemotherapy or hormone therapy in recurrent low-grade serous ovarian cancer, the first positive randomised trial in this slow-growing, chemotherapy-resistant disease.
Phase 2/3 trial of 260 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum randomised to trametinib or investigator's choice of letrozole, tamoxifen, weekly paclitaxel, pegylated liposomal doxorubicin or topotecan.
Median progression-free survival was 13.0 versus 7.2 months (hazard ratio 0.48) and response 26 versus 6 percent; skin rash, anaemia and hypertension were common with trametinib.
MEK inhibition is a standard option for recurrent low-grade serous ovarian cancer, and the trial validated the MAPK pathway as the disease's therapeutic target, now extended by avutometinib-defactinib.