Content area
Full Text
Introduction
Lung cancer is one of the leading causes of cancer-associated mortality globally, with a poor prognosis and a 5-year survival rate of <10% in patients with advanced-stage cancer, according to an international surveillance published in 2016 (1). Recent advancements in molecular targeted therapies for oncogenic driver mutations of advanced non-small cell lung cancer (NSCLC) have improved the prognosis in those individuals with tumors that express the appropriate molecular targets for inhibitory agents (2). However, the majority of patients with advanced NSCLC do not possess any molecular aberrations that can be targeted by any current agents. Therefore, further studies are required to identify and establish novel agents and concepts for molecular targeted therapy.
Antibody-mediated blockade of the interaction between programmed cell death-1 (PD-1) and activated cytotoxic T lymphocytes (CTLs), and between programmed cell death ligand-1 (PD-L1) and tumor cells, has exhibited significant clinical efficacy in a number of types of cancer, including NSCLC. Antibody-mediated blockade inactivates the tumoricidal activity of CTLs and therefore allows tumor cell immune evasion. Immune checkpoint inhibitors (ICIs) nivolumab, pembrolizumab and atezolizumab are currently approved for treating advanced-stage NSCLC. The CheckMate-017 (3), CheckMate-057 (4), KEYNOTE-010 (5) and OAK (6) trials demonstrated the superiority of these agents over docetaxel, which was the standard care for second-line therapy. However, the response to ICIs is only ~20%. In immunohistochemistry, despite the fact that PD-L1 has been approved as a biomarker, it is not sufficient for predicting the response to ICIs.
Efficacy of ICIs could be influenced not only by the intrinsic factors of patients, but also by extrinsic factors. Increasing focus has been placed on the role of gut microbiota in shaping systemic immune responses (7–9). Antibiotics cause changes in the gut microbiota (10–12) that may influence the efficacy of ICIs (13,14). A recent study indicated that prior use of antibiotics negatively influenced the efficacy of ICIs in the clinical settings (15). Using a prospective observational database, the present study performed a retrospective analysis to examine the influence of antibiotics on the clinical outcomes of patients treated with nivolumab for advanced NSCLC.
Materials and methods
Database acquisition
Clinical data from 90 patients with advanced NSCLC were retrospectively analyzed. Patients were treated with nivolumab as the second or later line of chemotherapy at the Tokyo...