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Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping
Racheal Louise Johnson1, Subhasheenee Ganesan1, Amudha Thangavelu1
1Department of Gynaecological Oncology, St James's University Hospital, Leeds LS9 7TF, UK.
Abstract:
Results of recent clinical trials using the immune check point inhibitors (ICI) pembrolizumab or dostarlimab with/without lenvatinib has led to their approval for specific molecular subgroups of advanced recurrent endometrial cancer (EC). Herein, we summarise the clinical data leading to this first tissue-agnostic approval. As this novel therapy is not yet available in the United Kingdom standard care setting, we explore the strengths, weaknesses, opportunities, and threats (SWOT) of ICI treatment in EC. Major databases were searched focusing on clinical trials using programmed cell death protein 1 (PD-1) and its ligand (PD-L1) ICI which ultimately contributed to anti-PD-1 approval in EC. We performed a data quality assessment, reviewing survival and safety analysis. We included 15 studies involving 1609 EC patients: 458 with mismatch repair deficiency (MMRd)/microsatellite instability-high (MSI-H) status and 1084 with mismatch repair proficiency/microsatellite stable (MMRp/MSS) status. Pembrolizumab/dostarlimab have been approved for MMRd ECs, with the addition of lenvatinib for MMRp cases in the recurrent setting. Future efforts will focus on the pathological assessment of biomarkers to determine molecular phenotypes that correlate with response or resistance to ICI in order to identify patients most likely to benefit from this treatment.
Insights
Immune checkpoint inhibitors (ICIs) like pembrolizumab are now approved for advanced recurrent endometrial cancer (EC) in specific molecular subgroups. This review examines the clinical data and SWOT analysis for ICI treatment in EC, particularly in the UK.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Advanced recurrent endometrial cancer (EC) treatment landscape is evolving with new therapeutic options.
- Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have shown efficacy in specific EC molecular subgroups.
- Recent approvals of pembrolizumab and dostarlimab, with or without lenvatinib, mark a significant advancement.
Purpose of the Study:
- To summarize clinical trial data supporting the tissue-agnostic approval of ICIs in advanced recurrent EC.
- To conduct a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of ICI treatment for EC in the UK context.
- To review the evidence base for anti-PD-1 therapy in EC.
Main Methods:
- Systematic search of major databases for clinical trials involving PD-1/PD-L1 ICIs in EC.
- Inclusion of 15 studies with 1609 EC patients (458 MMRd/MSI-H, 1084 MMRp/MSS).
- Data quality assessment focusing on survival and safety analyses.
Main Results:
- Pembrolizumab/dostarlimab approved for mismatch repair deficient (MMRd) EC.
- Lenvatinib in combination with ICIs approved for mismatch repair proficient (MMRp) advanced recurrent EC.
- Significant survival benefits observed in specific molecular subgroups.
Conclusions:
- ICI therapy represents a breakthrough for specific molecular subtypes of advanced recurrent EC.
- Further research is needed to identify biomarkers predicting response or resistance to ICI therapy.
- Integration of ICI treatment into standard care requires careful consideration of its SWOT profile.
