PD-1/PD-L1 inhibitor therapy: transitioning from a second-line to a first-line therapy for non-small cell lung cancer

Recently, monoclonal antibodies targeting the programmed death 1 (PD-1)/PD ligand 1 (PD-L1) pathway have dramatically changed the treatment paradigm for non-small cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been validated as second-line therapies for NSCLC, and are now being actively investigated as first-line therapies. In this paper, current data and future strategies for their use in first-line therapy are reviewed. There are five PD-1/PD-L1 inhibitors in development for NSCLC. Among them, three drugs (nivolumab, pembrolizumab, and atezolizumab) have been approved as second-line therapies for NSCLC in the United States. As a first-line therapy, pembrolizumab successfully showed superiority over platinum-based doublet chemotherapy in a strongly PD-L1-positive NSCLC group, while nivolumab failed to show efficacy as a first-line therapy. Currently, five PD-1/PD-L1 inhibitors are being tested as a first-line therapy for NSCLC in more than 10 phase III studies, with various study designs. Although it is not yet clear whether PD-1/PD-L1 inhibitors should be used as a monotherapy or in combination according to PD-L1 expression in first-line therapies, these promising drugs may play an important role in clinical practice as a first-line therapy for NSCLC in the near future