Regression of Chemotherapy-Resistant Polymerase ε (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab
作者： Alessandro D. Santin , Stefania Bellone , Natalia Buza , Jungmin Choi , Peter E. Schwartz
DOI: 10.1158/1078-0432.CCR-16-1031
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摘要: Purpose: The management of endometrial carcinoma no longer amenable to treatment with surgery or radiotherapy has not improved significantly modern chemotherapy. Alternative therapeutic options are desperately needed. Experimental Design: We describe 2 heavily pretreated patients recurrent disease refractory surgery, radiotherapy, and chemotherapy who were treated the anti–PD-1 immune checkpoint inhibitor nivolumab. Results: Patient #1 harbored an ultra-mutated tumor (mutation load/MB = 117.3, total mutations 4,660) driven by mutation in exonuclease domain DNA polymerase e gene. #2 a hyper-mutated 33.5, 1,037) due germinal MSH6 gene mutation. Both demonstrated remarkable clinical response Patients9 responses remain unchanged at time writing this report, grade 3 higher side effects reported date. Conclusions: Anti–PD-1 inhibitors represent novel option for recurrent/metastatic, ultra/hyper-mutated human tumors salvage treatment. Clin Cancer Res; 22(23); 5682–7. ©2016 AACR. See related commentary Piulats Matias-Guiu, p. 5623
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