Immunotherapy in non-small cell lung cancer: Update and new insights

BACKGROUND: The treatment of non-small-cell lung carcinoma (NSCLC) has changed markedly in recent years as a result of two major treatment milestones: Targeted therapy and immunotherapy. Since 2015, immunotherapy has been changing the paradigm of NSCLC treatment in different settings and has contributed to improve the quality of life of these patients. The most widely used immunotherapy strategy in clinical practice is currently PD-1 and CTLA-4 immune checkpoint inhibition-based immunotherapy. Initial successful results came from an improvement in overall survival for pretreated patients, and immunotherapy subsequently moved to a first-line palliative setting as monotherapy, in combination with chemotherapy or as double-checkpoint inhibition. With regard to earlier stages, consolidation immunotherapy after chemoradiation has also changed the paradigm of unresectable NSCLC, with marked benefits in terms of disease-free and overall survival. During the last few years, efforts have focused on the introduction of immunotherapy in earlier stages as neoadjuvant treatment for potentially resectable tumors and in an adjuvant setting, with some very promising results. AIM: In this manuscript, we provide both an agile and thorough review of the role of immunotherapy in non-small cell lung cancer, a critical analysis of the most important studies, current indications, the role of biomarkers, new insights, and future challenges. RELEVANCE FOR PATIENTS: Immunotherapy has revolutionized the treatment of non-small cell lung cancer patients reaching better survival outcomes in first and second palliative setting and in unresectable stage III tumors. Next year’s immunotherapy will also introduce in earlier stages. Through an extensive knowledge of the mechanisms of action and of immunotherapy-based studies, the best treatment alternative can be offered to patients, helping to improve their survival and cure rates.