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 - 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 -