Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer

Ann Oncol. 2024 May;35(5):414-428. doi: 10.1016/j.annonc.2024.02.006. Epub 2024 Feb 29.

Abstract

Background: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed.

Materials and methods: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer.

Results: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low.

Conclusions: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.

Keywords: chemotherapy; endometrial cancer; first line; immunotherapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Meta-Analysis

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / immunology
  • Endometrial Neoplasms* / pathology
  • Endometrial Neoplasms* / therapy
  • Female
  • Humans
  • Immunotherapy* / methods
  • Microsatellite Instability
  • Neoplasm Metastasis
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic

Associated data

  • ClinicalTrials.gov/NCT04269200
  • ClinicalTrials.gov/NCT03603184