Historically, lung cancer was long considered a poorly immunogenic malignancy. 
In recent years, however, immune checkpoint inhibitors have emerged as promising 
therapeutic agents in non-small cell lung cancer (NSCLC). To date, the best 
characterized and most therapeutically relevant immune checkpoints have been 
cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell 
death protein-1 (PD-1) pathway. In early studies, PD-1/programmed cell death 
ligand-1 (PD-L1) inhibitors demonstrated promising antitumor activity and 
durable clinical responses in a subset of patients. Based on these encouraging 
results, multiple different PD-1/PD-L1 inhibitors have entered clinical 
development, and two agents (nivolumab and pembrolizumab) have gained regulatory 
approval in the United States for the treatment of NSCLC. In several large, 
randomized studies, PD-1/PD-L1 inhibitors have produced significant improvements 
in overall survival compared with single-agent docetaxel delivered in the 
second-line setting, effectively establishing a new standard of care in NSCLC. 
In the present report, we provide an overview of the rationale for checkpoint 
inhibitors in lung cancer, recent clinical trial data, and the need for 
predictive biomarkers.
THE ONCOLOGIST: 2017;22:81-88 IMPLICATIONS FOR PRACTICE: Strategies targeting 
negative regulators (i.e., checkpoints) of the immune system have demonstrated 
significant antitumor activity across a range of solid tumors. In non-small cell 
lung cancer (NSCLC), programmed cell death protein-1 (PD-1) pathway inhibitors 
have entered routine clinical use because of the results from recent randomized 
studies demonstrating superiority against single-agent chemotherapy in 
previously treated patients. The present report provides an overview of immune 
checkpoint inhibitors in lung cancer for the practicing clinician, focusing on 
the rationale for immunotherapy, recent clinical trial data, and future 
directions.