To summarize the application of immune checkpoint inhibitors (ICIs) in gynecologic cancers and explore combination strategies with other therapies.
Approach:
Combination Strategies: The review focuses on combining ICIs with chemotherapy, radiotherapy, PARP inhibitors, and anti-angiogenic agents to enhance efficacy.
Key Findings:
ICIs have shown promise in gynecologic cancers, particularly in endometrial cancer with the MSI-H/dMMR subtype, as evidenced by the KEYNOTE-158 trial.
Response rates to ICI monotherapy are low in most gynecologic cancers, particularly in MSS or pMMR endometrial cancers, where they are typically below 10-15%.
Ovarian cancer presents significant challenges due to an immunosuppressive tumor microenvironment and low response rates to ICIs, with most patients eventually developing platinum resistance.
Interpretation:
Combination therapies aim to overcome the limitations of single-agent ICIs by synergistically remodeling the tumor immune microenvironment.
Limitations:
Current challenges include drug resistance, adverse events, and the need for reliable biomarkers, as well as the complexity of the tumor immune microenvironment which complicates treatment optimization.
Conclusion:
Further research is needed to optimize ICI-based combination therapies in clinical practice, particularly in understanding the tumor immune microenvironment and developing reliable biomarkers.
