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Clin Cancer Res. 2016 Dec 1;22(23):5682-5687. Epub 2016 Aug 2.

Regression of Chemotherapy-Resistant Polymerase ε (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab.

Author information

1
Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut. alessandro.santin@yale.edu.
2
Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.
3
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
4
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
5
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut.

Abstract

PURPOSE:

The management of endometrial carcinoma no longer amenable to treatment with surgery or radiotherapy has not improved significantly with modern chemotherapy. Alternative therapeutic options are desperately needed.

EXPERIMENTAL DESIGN:

We describe 2 heavily pretreated patients with recurrent disease refractory to surgery, radiotherapy, and chemotherapy who were treated with 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 the exonuclease domain of the DNA polymerase ε gene. Patient #2 harbored a hyper-mutated tumor (mutation load/MB = 33.5, total mutations = 1,037) due to a germinal MSH6 gene mutation. Both patients demonstrated a remarkable clinical response to the anti-PD-1 immune checkpoint inhibitor nivolumab. Patients' clinical responses remain unchanged at the time of the writing of this report, with no grade 3 or higher side effects reported to date.

CONCLUSIONS:

Anti-PD-1 inhibitors represent a novel treatment option for recurrent/metastatic, ultra/hyper-mutated human tumors refractory to salvage treatment. Clin Cancer Res; 22(23); 5682-7. ©2016 AACRSee related commentary by Piulats and Matias-Guiu, p. 5623.

PMID:
27486176
PMCID:
PMC5135588
DOI:
10.1158/1078-0432.CCR-16-1031
[Indexed for MEDLINE]
Free PMC Article

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