Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer

Abstract

Endometrial cancer is the most common cancer of the female reproductive organs. The American Cancer Society estimates that there will be over 65,950 new cases diagnosed in 2022. According to the National Comprehensive Cancer Network (NCCN) Guidelines, response rates in the front-line setting are approximately 40% to 62%. Prior to the recent U.S. Food and Drug Administration (FDA) approvals of immunotherapy, there had been no standard of care for women after failing front-line carboplatin and paclitaxel. In May 2017, the FDA approved single-agent pembrolizumab in microsatellite instability high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer patients following failure of systemic therapy. Then, in September 2019, the FDA approved pembrolizumab and lenvatinib for women who are not MSI-H or are MMR-proficient. This approval was based on KEYNOTE-146 and Study 111. Among 94 non-MSI-H women, 80% of those treated with pembrolizumab and lenvatinib had tumor shrinkage, and 38.3% had objective response by RECIST 1.1 as assessed by an independent radiology committee. The median duration of response was not reached, with 69% being progression free at 6 months. Grade 3/4 treatment-related adverse events (AEs) occurring in > 20%, including fatigue, hypertension, and gastrointestinal AEs. With supportive care, early identification, and intervention, the side effect profile was manageable, with only 21% discontinuing treatment due to AEs.

Figure 1

Algorithm for advanced/metastatic endometrial cancer based on tumor characteristics. EC = endometrial cancer; MSI-H = microsatellite instability high; MSS = microsatellite stable; TMB-H = tumor mutational burden high. Information from NCCN (2022).