557P Tumour mutation burden is a dispensable test in endometrial carcinoma patients whose molecular classification is known

Abstract

The panel of NCCN Guidelines recommend that Pembrolizumab is useful in patients of recurrent, metastatic, or high-risk endometrial carcinoma with TMB-H or MSI-H at second-line therapy according to the finding of KEYNOTE158, which makes TMB (tumor mutation burden) a key biomarker for the immunotherapy of endometrial carcinoma. TMB is typically calculated from data of whole exome sequencing or targeted sequencing of a panel of a few hundred genes, which means great economic burden for patients. In the initial design of molecular classification, mutation frequency served as one of the important references, thus we explored the proportion of TMB-H patients in subtypes. Publicly available data from publicly available data from the Cancer Genome Atlas (n=507) was analyzed to define the subtypes and calculate the TMB. We also retrospectively analyzed 79 endometrial carcinoma patients (WSB cohort) who performed NGS (733 gene panel) and evaluated for subtypes and TMB. We adopted two methods to define TMB-H and non-TMB-H. In method one, we set cutoff as 10, the same as KEYNOTE158, and the patient with TMB higher than 10 is considered to be a TMB-H patient. According to method one, POLE-mut and MSI-H endometrial carcinoma account for 96.76% (179/185) of TMB-H patients in TCGA cohort and 96.15% (25/26) in WSB cohort. In method two, patients who ranked in the top quartile of TMB were considered as TMB-H. We found that 96.85% (123/127) and 100% (20/20) of TMB-H patients in TCGA and WSB cohort were POLE-mut and MSI-H endometrial carcinoma. In both methods, only one POLE-mut patients (1/49) were non-TMB-H in TCGA cohort and all POLE-mut patients in WSB cohort were TMB-H (3/3). For patients whose molecular classification is known, TMB detection is a dispensable test. Immunotherapy may be admissible for POLE-mut and MSI-H patients without the performance of TMB detection.