Trametinib as a new standard of care option for low-grade serous ovarian cancer

Important contributions of Edinburgh investigators to the GOG281/LOGS clinical trial that offers new standard of care option for women with progressive or relapsed low-grade serous ovarian cancer.

Ovarian cancer, or cancer of the ovaries, forms when abnormal cells in the ovary or fallopian tube begin to grow and divide in an uncontrolled way. It is one of the most common types of cancer in women with approximately 7,500 new cases (that is ~21 every day!) and over 4,000 ovarian cancer deaths in the UK every year.

Epithelial ovarian cancer is the most common type of ovarian cancer and has five different histological subtypes: high-grade serous, endometrioid, clear cell, mucinous, and low-grade serous. Low-grade serous ovarian cancer (LGSC) is a rare, slow-growing cancer that is generally resistant to cytotoxic chemotherapy. Until now, LGSC treatment recommendations extrapolated results from historical randomized studies dominated by high-grade serous ovarian cancer despite clearly discrete biology and clinical behaviour. There were no positive randomised clinical studies reported in LGSC to date.

This situation has just changed thanks to results of the GOG 281/LOGS trial – a randomised, open-label phase 2/3 trial comparing treatment with MEK inhibitor trametinib to physician’s choice standard of care in recurrent LGSC. MEK inhibitors are chemicals that inhibit the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. These enzymes play important role in cellular signalling and their inhibitors are already being used to treat some cancers, including certain types of melanoma, lung cancer and thyroid cancer.

The study titled “Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): a randomised, open-label phase 2/3 trial” and published in medical journal The Lancet summarises work conducted across 84 centres in the United States and the United Kingdom. The trial overcame challenges associated with patient recruitment (common for rare cancers) providing the first ever positive prospective randomised clinical study reported for LGSC. The work demonstrated that trametinib reduced the rate of disease progression or death by 52% compared to investigator’s choice of endocrine therapy or chemotherapy. Trametinib also increased the probability of response to therapy four-fold and showed a trend toward an overall survival benefit. Based on the trial’s findings, trametinib should be considered a new standard of care option for women with progressive or relapsed LGSC.

Edinburgh investigators played important role in the study with five Edinburgh researchers: Michael Churchman, Ailith Ewing, Robert L. Hollis, C. Simon Herrington, Charlie Gourley listed as authors on the publication and Professor Charlie Gourley acting as the UK Lead for the trial.

The GOG281/LOGS trial represents a significant break-through for low-grade serous ovarian cancer research and we hope that its findings will soon be adopted by the medical community providing a new standard of care and benefiting patients

Professor Charlie Gourley, Nicola Murray Centre for Ovarian Cancer ResearchCancer Research UK Edinburgh Centre, University of Edinburgh

The tissue origins and major molecular pathway alterations in different types of ovarian epithelial cancer. [from Shih et al. Am J Pathol. 2021;191:26-39]

Trametinib as a new standard of care option for low-grade serous ovarian cancer

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