Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma

被引:19
作者
Davar D. [1 ]
Socinski M.A. [1 ,3 ]
Dacic S. [2 ]
Burns T.F. [1 ,4 ]
机构
[1] University of Pittsburgh Medical Center, Division of Hematology-Oncology, Department of Medicine, Pittsburgh, PA
[2] University of Pittsburgh Medical Center, Division of Anatomic Pathology, 200 Lothrop Street, Office: PUH C608, Pittsburgh, 15213, PA
[3] University of Pittsburgh Cancer Institute, Division of Hematology-Oncology, 5150 Centre Avenue, 5th floor, Pittsburgh, 15232, PA
[4] University of Pittsburgh Cancer Institute, Division of Hematology-Oncology, 5117 Centre Avenue, Office: Suite 2.18e, Pittsburgh, 15232, PA
关键词
Adenocarcinoma; KRAS mutant; Lung cancer; Nivolumab; Programmed death receptor-1 (PD-1);
D O I
10.1186/s40164-015-0029-7
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学科分类号
摘要
The programmed death 1 (PD-1) receptor is expressed by activated T-cells and engaged by ligands PD-L1 and PD-L2 normally expressed by infiltrating immune cells in response to viral infection. The PD-1/PD-L1 axis is a negative inhibitory pathway that down-regulates T-cells but is also used by tumors to evade anti-tumor immunity. Antibodies targeting PD-1/PD-L1 axis are capable of restoring functional anti-tumor immunity and have demonstrated efficacy in a broad range of tumor types including non-small cell lung cancer in both squamous and adenocarcinoma histologies. Ongoing issues affecting clinical development of these agents include assessment of response, optimal duration of therapy in excellent responders, predictive biomarkers and mechanisms of resistance. In this report, we describe a patient with advanced KRAS mutant heavily pretreated pulmonary adenocarcinoma who developed an excellent response after a single-dose of nivolumab. Pre-treatment tumor was found to have moderate CD3 and PD-L1 positivity by immunohistochemical staining. Evaluation of exceptional responders and non-responders are critical to furthering our understanding of the mechanisms of action (and resistance) to these agents. © 2015 Davar et al.
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