Immune Checkpoint Inhibitors in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer

Surgical resection ± chemotherapy ± radiation or stereotactic body radiation therapy (SBRT) are established treatment modalities for resectable stage non-small cell lung cancer (NSCLC), and concurrent chemotherapy with radiation is the therapy of choice for unresectable locally advanced disease. Despite treatment with curative intent, most patients subsequently relapse and develop distant disease. Treatment with checkpoint inhibitors represents a major advancement in the treatment of metastatic NSCLC. Therapy against programed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) is associated with a significant improvement in overall survival in stage IV disease, and these results have led to a great interest in evaluating these agents in earlier-stage NSCLC. The preliminary data from ongoing trials suggest that the integration of checkpoint blockage into the treatment of early-stage and locally advanced NSCLC is safe, tolerable, and has the potential to improve outcomes without adding substantial toxicity. In the current review, we provide an overview of the emerging data on the role of PD-1/PD-L1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors in the treatment of early-stage and locally advanced NSCLC, with a focus on ongoing clinical trials and combination strategies.