title: Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma.
abstract: 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.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA USA.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Davar
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA USA ; Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Office: Room 556, 5th floor, Pittsburgh, PA 15232 USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.affiliation: Division of Anatomic Pathology, University of Pittsburgh Medical Center, 200 Lothrop Street, Office: PUH C608, Pittsburgh, PA 15213 USA.
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA USA ; Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Office: Suite 2.18e, Pittsburgh, PA 15232 USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Burns
keywords: Adenocarcinoma; KRAS mutant; Lung cancer; Nivolumab; Programmed death receptor-1 (PD-1)