Santin Alessandro D, Bellone Stefania, Buza Natalia, Choi Jungmin, Schwartz Peter E, Schlessinger Joseph, Lifton Richard P
Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Clin Cancer Res. 2016 Dec 1;22(23):5682-5687. doi: 10.1158/1078-0432.CCR-16-1031. Epub 2016 Aug 2.
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.
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.
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.
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.
对于不再适合手术或放疗的子宫内膜癌患者，现代化疗并未显著改善其治疗效果。迫切需要其他治疗选择。
我们描述了2例经过大量前期治疗的复发性疾病患者，这些患者对手术、放疗和化疗均耐药，接受了抗PD-1免疫检查点抑制剂纳武单抗治疗。
患者1的肿瘤存在超突变（突变负荷/百万碱基 = 117.3，总突变数 = 4660），由DNA聚合酶ε基因外切酶结构域的突变驱动。患者2的肿瘤存在高突变（突变负荷/百万碱基 = 33.5，总突变数 = 1037），原因是胚系MSH6基因突变。两名患者对抗PD-1免疫检查点抑制剂纳武单抗均表现出显著的临床反应。在撰写本报告时，患者的临床反应保持不变，迄今为止未报告3级或更高等级的副作用。
抗PD-1抑制剂代表了一种针对复发/转移性、超/高突变且对挽救治疗耐药的人类肿瘤的新型治疗选择。《临床癌症研究》；22(23)；5682 - 7。©2016美国癌症研究协会。见Piulats和Matias-Guiu的相关评论，第5623页。
