GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer
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.
Overview
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.
- Median progression-free survival 13.0 vs 7.2 months; hazard ratio 0.48.
- Objective response 26 percent vs 6 percent.
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.
- Open-label; overall survival not significantly different with crossover.
- Toxicity led to dose reductions in many patients.