Approaches to optimize the benefits of immunotherapy and immunotherapy combinations across endometrial cancer types

Area of Science:

• Gynecologic Oncology
• Cancer Immunology
• Molecular Oncology

Background:

• Endometrial cancer (EC) incidence and mortality are increasing, affecting younger populations.
• Molecular characterization, like mismatch repair deficiency (dMMR), predicts response to immune checkpoint inhibitors (ICI) in some EC cases.
• Immunotherapy response is limited in other EC molecular subtypes, necessitating further research.

Purpose of the Study:

• To explore novel strategies for optimizing immunotherapy in diverse endometrial cancer molecular types.
• To discuss the timing and sequencing of immunotherapy with other treatment modalities.
• To identify potential novel immunotherapy combinations and approaches to overcome resistance.

Main Methods:

• Review of key background studies and preclinical observations.
• Analysis of strategies to overcome inherent immunotherapy resistance in EC.
• Evaluation of methods to enhance clinical response by combining ICI with standard treatments.

Main Results:

• Identified limitations in predictive biomarkers for immunotherapy response beyond dMMR.
• Outlined approaches to leverage ICI for augmenting response to standard EC treatments.
• Considered optimal timing and sequencing for re-exposure to ICI treatments.

Conclusions:

• New therapeutic concepts are emerging to enhance immunotherapy efficacy across all EC molecular subtypes.
• Optimizing immunotherapy application requires considering molecular profiles, treatment sequencing, and novel combinations.
• Potential clinical trial concepts are under development based on these discussions.