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Emerging Immunotherapies in the Treatment of Non–small Cell Lung Cancer (NSCLC): The Role of Immune Checkpoint Inhibitors

Immune checkpoint inhibition as a new treatment approach is undergoing extensive investigation in non–small cell lung cancer (NSCLC) and other malignancies. Unlike standard chemotherapy or targeted agents, which act directly on the tumor cells, immune checkpoint inhibitors work by restoring the immune system’s capacity to eradicate tumors. Agents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte–associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A). Preliminary evidence shows activity for these agents in NSCLC as monotherapy or in combination with chemotherapy. This article reviews the immune checkpoint inhibitors and the available data to date on their use in lung cancer. Clinical implications for the use of these therapies in NSCLC are discussed as they relate to their novel mechanisms of action, response patterns, and safety profiles.