Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

Abstract

Simple Summary Moving from the achievements of immune checkpoint inhibitors in metastatic lung cancer, the great promise of immunotherapy in resectable early-stage is to make a disease, often lethal until now for frequent post-surgery relapses, more curable. This review focuses on role of immunotherapy in early-stage non-small cell lung cancer. We summarize biological rationale, findings from clinical trials of adjuvant and neoadjuvant immune checkpoint inhibitors, questions about biomarkers and choice of endpoints, aiming to provide up-to-date information useful for clinical decision making. Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.