Recent developments in the use of immunotherapy in non-small cell lung cancer

Abstract

Introduction: Targeted therapies have significantly improved the prognosis of subsets of patients with advanced non-small-cell lung cancer (NSCLC) harboring somatically activated oncogenes, such as mutant EGFR and rearranged ALK. However, the efficacy of these agents is limited by the development of acquired resistance which occurs after variable periods of time. Therefore, there is an urgent need for novel therapeutic strategies to achieve long lasting disease control, as well as new therapies for those patients without targetable driver mutations. A deeper understanding of interactions between the immune system and tumor cells has led to the development of a number of immunotherapeutic agents.

Areas covered: We review current data on immunotherapy for lung cancer treatment, with a focus on checkpoint inhibitors and therapeutic vaccines. References for this review were identified through searches of PubMed, congress proceedings and reference lists from key original and review papers. Expert commentary: While most vaccines have been unsuccessful, inhibitors of specific immune checkpoints, including CTLA-4 and PD-1/PD-L1 pathway, have shown significant clinical activity and manageable toxicities and recently, two anti-PD-1 monoclonal antibodies have been approved by the FDA for treatment of patients with advanced NSCLC. Identification of reliable predictive biomarkers for patient selection and novel rational combinations are currently active areas of research to further improve the efficacy of immunotherapy.

Keywords: Non-small-cell lung cancer; cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); immune checkpoint inhibitors; programmed cell death ligand-1 (PD-L1); programmed cell death protein-1 (PD-1).