Abstract
Currently, treatment options for patients with advanced or recurrent endometrial cancer remain limited. The current standard of care treatment for advanced endometrial carcinoma is a platinum doublet chemotherapy. Second-line treatment options overall are very limited. There is no optimal treatment option for patients who show disease progression with first-line therapy. Therefore, novel and more efficacious therapies for patients with advanced or recurrent disease are needed. Immune checkpoint inhibitors have demonstrated a very impressive safety profile and anti-tumor activity in patients with programmed death-ligand 1 (PD-L1) positive endometrial cancer who were pre-treated with chemotherapy. We have done a detailed review of the literature to emphasize the role of immune checkpoint inhibitors in the treatment of metastatic or recurrent endometrial cancer.
Highlights
BackgroundEndometrial cancer is the most common malignancy of the female genital tract in the United States
The main risk factors associated with developing endometrial cancer include increased estrogen exposure, complex atypical hyperplasia, tamoxifen use, Lynch syndrome, and diabetes mellitus
Type 1 carcinoma is mediated by estrogen and has an increased percentage of mutations as well as defects in mismatch repair (MMR) genes resulting in microsatellite instability (MSI)
Summary
Endometrial cancer is the most common malignancy of the female genital tract in the United States. The role of PD-1 and PD-L1 blockade in advanced endometrial cancers can be significant, and there have been some phase 1 and phase 2 studies done to evaluate the anti-tumor efficacy, safety, and survival analysis in this population. Recent reports of responses with PD-1 inhibition in endometrial cancers with high mutation rates suggest that anti-tumor activity with PD-1 monotherapy may be mainly driven by preexisting neoantigen reactive T cells. Mehnert et al did a case study to study the role of genomic mutations in patients with PD-1 positive endometrial cancer They identified a single patient that showed rapid clinical improvement once pembrolizumab treatment was initiated, exhibiting a partial response after eight weeks and sustaining the response for more than 14 months [27]. These exceptional results support the theory that the presence of POLE mutations may aid in identifying patients for whom pembrolizumab may be effective, a concept that should be investigated further
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