Immunotherapy in endometrial cancer

Abstract

The Cancer Genome Atlas (TCGA) endometrial cancer data expanded our knowledge about the role of different immunotherapeutic approaches based on molecular subtypes. Immune checkpoint inhibitors demonstrated distinct antitumor activities as monotherapy or in combination. In microsatellite unstable (microsatellite instability-high) endometrial cancer, immunotherapy with immune checkpoint inhibitors showed promising single agent activity in recurrent settings. Different strategies are needed to enhance the response or reverse resistance to immune checkpoint inhibitors, or both, in microsatellite instability-high endometrial cancer. On the other hand, single immune checkpoint inhibitors showed underwhelming efficacy in microsatellite stable endometrial cancer but this was significantly improved using a combination approach. Furthermore, studies are also needed to improve response along with ensuring safety and tolerability in microsatellite stable endometrial cancer. This review summarizes the current indications of immunotherapy for the treatment of advanced and recurrent endometrial cancer. We also outline potential future strategies for an immunotherapy based combination approach in endometrial cancer to combat resistance or enhance response to immune checkpoint inhibitors, or both.

Keywords: Endometrial Neoplasms.

Figure 1

Treatment landscape in endometrial cancer. *Advanced stage/metastatic endometrial cancer or serous histology. #Pembrolizumab+lenvatinib. §Ongoing research. Anti-PD1, anti-programmed cell death protein 1; EC, endometrial cancer; FDA, Food and Drug Administration; IHC, immunohistochemistry; MSI-H, microsatellite instability-high; MSS, microsatellite stable; PCR, polymerase chain reaction; RT, radiation.

Figure 2

Food and Drug Administration approvals summary for immune checkpoint inhibitors based on microsatellite instability and tumor mutational burden status in solid tumors. *KEYNOTE-16; **KEYNOTE-158; ***KEYNOTE-146 and KEYNOTE-775; §CheckMate142; !Garnet. CRC, colorectal cancer; dMMR, deficient mismatch repair; MSI-H, microsatellite instability-high; MSS, microsatellite stable; TMB, tumor mutational burden.