Immunotherapy for endometrial cancer.

Area of Science:

• Oncology
• Genomics
• Immunotherapy

Background:

• Advanced recurrent endometrial cancer (EC) presents a significant clinical challenge with limited treatment options.
• Genomic classification of EC into four subtypes (POLE, MSI-H, copy number low, copy number high) impacts prognosis and treatment strategies.
• Endometrial cancer exhibits high PD-1 and PD-L1 expression, particularly in the MSI-high subtype, suggesting sensitivity to immune checkpoint inhibitors (ICIs).

Purpose of the Study:

• To review the evolving role of ICIs in the treatment of advanced recurrent endometrial cancer.
• To highlight the efficacy of pembrolizumab, alone and in combination, for EC treatment.
• To discuss the management of immune-related adverse events (irAEs) associated with ICI therapy.

Main Methods:

• Review of clinical trial data and literature on ICI therapy in recurrent endometrial cancer.
• Analysis of genomic classifications and their correlation with PD-L1 expression and treatment response.
• Evaluation of combination therapies involving ICIs, chemotherapy, and targeted agents like lenvatinib.

Main Results:

• Pembrolizumab demonstrated efficacy in MSI-high recurrent EC.
• The combination of pembrolizumab and lenvatinib significantly improved overall survival (OS) and progression-free survival (PFS) compared to chemotherapy in previously treated recurrent EC, irrespective of MSI status.
• ICI-based regimens are increasingly used in first-line settings, with ongoing trials comparing them to traditional chemotherapy.

Conclusions:

• ICIs, particularly pembrolizumab in combination with lenvatinib, represent a significant advancement in treating advanced recurrent endometrial cancer.
• Treatment individualization based on genomic classification, especially MSI status, is crucial.
• While effective, ICIs can cause immune-related adverse events (irAEs), necessitating prompt management, especially with combination therapies.