Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence

Abstract

Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.

Keywords: anti-programmed death-1; immunotherapy; nivolumab; non-small cell lung cancer.

Figure 1.

Mechanism of action of nivolumab. The TCR signaling pathway is a major component of immune defense against tumors. Under normal circumstances, TCR recognition of the MHC on APCs will trigger a cascade of events causing activation of T cells and thus immune response against tumor cells. This signal is inhibited by tumor cells with activation of the PD-1/PD-L1 inhibitor co-signaling pathway, which ameliorates T-cell activation. Nivolumab acts by binding onto the PD-L1 on T cells, thus preventing inhibitor co-signaling and restoring T-cell activation. APC, antigen presenting cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1, programmed death-1 ligand; TCR, T-cell receptor.