Do Not Forget about Hormonal Therapy for Recurrent Endometrial Cancer: A Review of Options, Updates, and New Combinations

SIMPLE SUMMARY: Endometrial cancer is the most common gynecologic cancer in the developed world and in the recurrent setting has a dismal prognosis. As the endometrium is a hormonally active tissue, hormonal therapy has long been an integral treatment modality. There are many options for hormonal therapy including progesterones, agents that target the estrogen pathway, and combinations with targeted therapies, which are described in detail in this review. High disease control rate, long duration of response, and easy tolerability make hormonal therapy an excellent option for patients with low-grade hormone receptor-positive disease who would like to avoid or cannot tolerate cytotoxic chemotherapy or other targeted therapies. ABSTRACT: Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.