Immune checkpoint inhibitors for recurrent endometrial cancer

Expert Rev Anticancer Ther. 2022 Mar;22(3):249-258. doi: 10.1080/14737140.2022.2044311. Epub 2022 Feb 24.

Abstract

Introduction: Endometrial cancer (EC) is the most common gynecologic malignancy. Outcomes for patients with advanced and/or recurrent disease have been modest with the use of chemotherapy. The approval of immune checkpoint inhibitors targeting PD-1 has recently revolutionized human cancer treatment. Recent trials with immune checkpoint inhibitors used alone or in combination with other agents, have demonstrated remarkable efficacy in the treatment of the all-comers EC patient population.

Areas covered: In this article, we review major clinical trials on PD-1/PD-L1 inhibitors in advanced and recurrent EC and discuss the response rates of these agents in the context of their genomic background.

Expert opinion: Immune checkpoint inhibitors have significantly changed our approach to the treatment of advanced/recurrent EC. Single agent anti-PD-1 regimens are highly effective in MMRd/MSI-H patients, but their clinical efficacy remains modest in MMR proficient/TMB low EC patients. Combination regimens that can decrease the tumor microenvironments immunosuppression and increase tumor immunogenicity represent a viable treatment option to broaden the activity of immune checkpoint inhibitors in advanced/recurrent EC patients. An increased understanding of the biomarkers of response and the molecular mechanisms of resistance to immune checkpoint inhibitors remains key for the next advancement of the field.

Keywords: Endometrial cancer; PD-1 inhibitor; PD-L1 inhibitor; immune checkpoint inhibitors; immunotherapy; targeted therapy.

Publication types

  • Review

MeSH terms

  • Endometrial Neoplasms* / drug therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immunotherapy
  • Microsatellite Instability
  • Neoplasm Recurrence, Local / drug therapy
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor