TY - JOUR
T1 - Regression of chemotherapy-resistant polymerase ϵ (POLE) ultra-mutated and MSH6 hyper-mutated endometrial tumors with nivolumab
AU - Santin, Alessandro D.
AU - Bellone, Stefania
AU - Buza, Natalia
AU - Choi, Jungmin
AU - Schwartz, Peter E.
AU - Schlessinger, Joseph
AU - Lifton, Richard P.
N1 - Funding Information:
This work was supported in part by grants from NIH U01 CA176067-01A1, the Deborah Bunn Alley Foundation, the Tina Brozman Foundation, the Discovery to Cure Foundation, and the Guido Berlucchi Foundation to Alessandro D. Santin. This investigation was also supported by NIH Research Grant CA-16359 from NCI. Richard Lifton is an Investigator of the Howard Hughes Medical Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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 e 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.
AB - 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 e 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.
UR - http://www.scopus.com/inward/record.url?scp=85006163806&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-16-1031
DO - 10.1158/1078-0432.CCR-16-1031
M3 - Article
C2 - 27486176
AN - SCOPUS:85006163806
SN - 1078-0432
VL - 22
SP - 5682
EP - 5687
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -