Exploring tumor mutational burden status and clinical benefit of immune checkpoint inhibitors in endometrial cancer

Abstract

Tumor mutations are key in the generation of anticancer immunity. Tumors with high mutational burden (TMB) are more likely to harbor high levels of neoantigens that make them targets of activated immune cells and thus may have superior and/or prolonged response to immune checkpoint inhibitors (ICI) when compared to TMB-low counterparts. A recently published biomarker analysis of KEYNOTE-158 reported that tumors with TMB-high status had a higher objective response to pembrolizumab monotherapy than non-TMB-high tumors leading to FDA approval of Pembrolizumab in TMB-high solid tumors. Importantly, among TMB-high responses, 57% had durable response >12 months. Reported objective response in endometrial cancer cohort was 46.6% in TMB-high (7/15) vs 4.9% (4/67) non-TMB high. In our study, we aimed to further investigate this identified association between TMB-high status and sensitivity to ICI in endometrial cancer by evaluating clinical benefit and duration of clinical benefit in TMB-high vs TMB-low patient groups.