Case Report: Immune Checkpoint Inhibitor Elicited Complete Response in a Heavily Pretreated Patient with Metastatic Endometrial Carcinoma with a High Tumor Mutation Burden (TMB)
Barve M, Adams N, Plato L, Dupler R,
Anand R, Jones J, Brown M, Stephens
PJ, Shiller SM, Senzer N, Nemunaitis
Correspondence Address :
Cancer Research Centers
12222 Merit Drive, Suite 1500, Dallas, Texas 75251
Tel: 214-658-1964, Fax: 214-658-1992
Received on: November 07 2017, Accepted on: November 28, 2017, Published on: December 06, 2017
Citation: Barve M , Adams N , Plato L , et al. (2017). Case Report: Immune Checkpoint Inhibitor Elicited Complete Response in a Heavily Pretreated
Patient with Metastatic Endometrial Carcinoma with a High Tumor Mutation Burden (TMB)
Copyright: 2017 Nemunaitis J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We report a unique case example of a patient with advanced metastatic endometrial cancer who failed standard of care options before presentation to our translational program for targeted experimental options. Molecular profile analysis (FoundationOneTM
testing, Cambridge, MA) of this patient revealed several genomic alterations potentially associated with therapeutic opportunities. In particular, the tumor mutation burden (TMB) and microsatellite instability (MSI) was high (>20 mutations load per megabase of DNA) with the presence of a MSH2 loss-of-function mutation and PD-L1 expression <1%. We hypothesized that this group of genomic aberrations would likely indicate an increased neoantigen load and consequently a heightened probability of sensitivity to immune checkpoint inhibitors. Therefore, the patient entered a phase I study of the immune checkpoint inhibitor durvalumab. This heavily pretreated patient achieved a complete and long lasting clinical response to immunotherapy with no significant side effects. Follow up analysis of 266 additional patients identified 29 with TMB >20 mutations (mu)/Mb DNA. Six of these received immunotherapy and all 6 demonstrated response whereas only 1 of 21 other high TMB patients who did not receive immunotherapy achieved response. Genomic analysis has emerged as an important predictive component to maximize proportionate therapeutic benefit to immunotherapy and to help prioritize amongst investigative therapeutic options when available.
Keywords: Tumor mutation burden, Molecular signal, Endometrial, Immunotherapy, checkpoint