Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC)

Abstract

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has become a "game changer" in the treatment of advanced non-small cell lung cancer (NSCLC). Its most clinically important advantage over traditional chemotherapy using cytotoxic agents are its long-term survival benefits, and some advanced NSCLC patients treated with an antibody against programmed cell death 1 (PD-1) have survived for 5 years or longer. Immune checkpoint inhibitors (ICIs) are also potentially useful for earlier-stage NSCLC when used in combination with surgery or radiotherapy. A recent clinical trial has shown that consolidation treatment with an antibody against a ligand of PD-1 (PD-L1) following chemo-radiotherapy significantly improves progression-free survival for patients with locally advanced NSCLC. However, current single-agent treatment with an anti-PD-1/PD-L1 antibody may provide significant survival benefits only in a small subset of patients. PD-L1 expression status on tumor cells is an approved biomarker to predict response to ICIs, but is not enough for optimal patient selection. To improve the therapeutic outcomes, development of novel biomarkers other than PD-L1 expression status is essential. Combination treatment strategies based on blockade of PD-1/PD-L1 may also be promising, and a variety of combinations, such as ICIs plus chemotherapy, are being examined in ongoing clinical trials. Here we review and discuss the current status and future perspectives of immunotherapy with ICIs.

Keywords: PD-1; PD-L1; cancer immunity; immune checkpoint; lung cancer.