The current status of immunotherapy using anti PD-1 or PD-L1 antibodies

Abstract

Background: Although lung cancer still has a high mortality rate, immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) and anti-programmed cell death-ligand 1 (PD-L1) antibodies are resulting in a paradigm shift in treatment strategy. Observation: T cells play an important role in cancer immunology; however, T cell immune activity is downregulated due to the binding of the PD-1 receptor that is expressed on T cells to its ligand, PD-L1, which is expressed on tumor cells. Anti-PD-1/PD-Ll antibodies block the binding of PD-1 to PD-L1 and thereby inhibit this downregulation of T cell activity. Nivolumab is an anti-PD-1 antibody. Phase III studies that compared nivolumab to docetaxel demonstrated the superiority of nivolumab in terms of the overall survival (OS) of previously treated squamous cell carcinoma (SQ), non-small cell lung cancer (NSCLC), and non-squamous cell carcinoma (NSQ) NSCLC patients. Pembrolizumab is another anti-PD-1 antibody, and a phase III study showed the superiority of pembrolizumab to docetaxel in terms of the OS of previously treated NSCLC patients. In addition, a phase III study that compared pembrolizumab to platinum-based combination chemotherapy showed that pembrolizumab significantly prolonged progression-free survival as well as OS in advanced NSCLC patients, and that PD-L1 was expressed on at least 50% of the tumor cells in the first line setting. Several anti-PD-L1 antibodies such as atezolizumab, durvalumab and avelumab are also being evaluated in various clinical studies. Conclusions: Anti-PD-1/PD-Ll antibodies represent key drugs for the standard therapy of NSCLC, both as a second-line and as a first-line therapy. However, other predictive biomarkers of immunotherapy are required.