Lung cancer is the leading cause of cancer-related deaths worldwide and is associated with poor 5-year outcomes, even among the 20% to 25% of patients who present with operable disease. Cisplatin-based adjuvant chemotherapy has long been the standard of care for patients with resected non-small cell lung cancer (NSCLC). With the incorporation of immunotherapy, however, the treatment paradigm for NSCLC has changed dramatically. The introduction of immune checkpoint blockade has improved clinical outcomes in multiple phase 2 and 3 trials in both the neoadjuvant and adjuvant setting, resulting in new US Food and Drug Administration approvals in the management of early-stage resectable lung cancer. This review explores the biological rationale for immune checkpoint blockade, both as monotherapy and in combination with chemotherapy, in conjunction with surgical management of patients with NSCLC. It also highlights the reported clinical trial data that have led to significant advances in the management of early-stage NSCLC. Additionally, this review summarizes ongoing key studies that will provide vital data on the clinical efficacy of these treatment approaches. The outcomes of ongoing trials and the associated biomarker-focused correlative studies will be critical to furthering the mechanistic understanding of immune checkpoint blockade in early-stage NSCLC. This, in turn, will help to uncover biomarkers of response and resistance in these patients.
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