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.