Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis

SIMPLE SUMMARY: This review will summarise the landmark clinical trials leading to the first tissue-agnostic approval of immune checkpoint inhibitors in specific molecular profiles of recurrent endometrial cancer (EC). As this treatment is a novel therapy and yet to be integrated into routine clinical use in the United Kingdom for EC patients, we will explore its strengths, including the ability to provide clinical survival benefit in patients with poor prognostic features, and its weaknesses, outlining immunotherapy toxicity and lack of availability for other molecular subgroups. We will define the opportunities this therapy presents, such as current trials investigating immunotherapy in combination with traditional therapy and/or novel targets, as well as threats to this treatment, such as financial implications and the practicalities of novel drug delivery and monitoring. 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.