Response to first line platinum-based chemotherapy in mismatch repair deficient (MMRd)/ microsatellite instability high (MSI-high) endometrial carcinoma

Gynecol Oncol. 2023 Feb:169:78-84. doi: 10.1016/j.ygyno.2022.11.029. Epub 2022 Dec 13.

Abstract

Background: Around 15% of metastatic endometrial carcinoma (EC) are MMRd/MSI-H improving response to immune checkpoint inhibitors (ICI). So far, few data existed considering the chemotherapy (CT) sensitivity in MMRd/MSI-H EC, especially response to first-line platinum-based treatment.

Patients and methods: We performed a multicentric retrospective analysis reporting the response to first line platinum CT in MMRd/MSI-H EC patients. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) with first line platinum-based CT.

Results: A total of 112 patients MMRd/MSI-H EC from 8 centers were identified. Median overall survival was 58.0 months (95% CI: 45.3-95.1). Among them, 78 patients received first line platinum CT in recurrent/metastatic setting. With a median follow up of 32.6 months (min: 0.03; max: 135.0), ORR and DCR (disease control rate) were 50% (95% CI: 38.5-61.5) and 68% (95% CI: 56.4-78.1), respectively. Median PFS and OS from first line platinum-based CT was 7.8 months (95% CI: 6.0-9.0) and 51.9 months (95% CI: 28.0-NE), respectively. Median PFS with ICI in second line (n = 48) was 10.7 months (95% CI: 3.4-NE) from ICI initiation.

Conclusion: ORR in first line metastatic MMRd/MSI-H EC is consistent with efficacy in an all comer metastatic EC population.

Keywords: Chemotherapy; DNA repair; Endometrial carcinoma; Immunotherapy; MMR; MMRd/MSI-H.

MeSH terms

  • Colorectal Neoplasms* / pathology
  • DNA Mismatch Repair
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / genetics
  • Female
  • Humans
  • Microsatellite Instability
  • Platinum / therapeutic use
  • Retrospective Studies

Substances

  • Platinum

Supplementary concepts

  • Turcot syndrome