BACKGROUND: Lung cancer is the most common cause of cancer-related death among 
males and the second leading cause among females globally. Checkpoint inhibitors 
re-engage the immune system to fight cancer. This review evaluates phase III 
data on the use of checkpoint inhibitors in the treatment of advanced NSCLC and 
addresses PD-L1 expression in predicting efficacy.
METHODS: Six phase III clinical trials investigating checkpoint inhibitors for 
NSCLC were identified through a search of PubMed (to November 15, 2016) and 
conference databases, with findings updated from a directed search of eligible 
studies conducted in January 2018.
RESULTS: Significant reductions in the risk of death ranging from 27% to 41% and 
were observed second-line and beyond. A relationship between PD-L1 expression 
and survival was apparent in most trials with optimal benefit for the highest 
expression levels (≥50%). Benefit was also observed at low or no PD-L1 
expression levels and in third-line in some studies. Significantly improved PFS 
was observed for pembrolizumab at high PD-L1 expression levels (≥50%) 
first-line. Immune-related adverse events associated with checkpoint inhibitors 
are tolerable and rates of pneumonitis may be lower among PD-L1 inhibitors. Use 
of checkpoint inhibitors for tumors with driver mutations should only be 
considered after all appropriate targeted therapy and chemotherapy have been 
exhausted. PD-L1 testing presents a valuable tool to guide treatment sequencing 
and we recommend use of agent-specific PD-L1 tests and respective scoring 
systems until a standardized, convenient and broadly applicable test is 
identified.
CONCLUSIONS: Checkpoint inhibitors represent a major advance in the treatment of 
advanced NSCLC and PD-L1 status can inform treatment decisions.