Abstract
Thyroid dysfunction is one of the major side effects associated with Pembrolizumab in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC). We performed a systematic review and meta-analysis of randomized clinical trials to determine its overall incidence. A literature search was conducted using the electronic database engines PubMed and Google Scholar from inception to March 2019. Eligible studies were prospective randomized clinical trials with advanced or metastatic NSCLC. The pooled incidence, risk ratio (RR), and 95% confidence interval (CI) of thyroid dysfunction were calculated using the random-effect model. Given the possibility of a between-study variance, we used the random-effect model rather than the fixed-effect model.A total of four studies, including 1603 patients, were selected for analysis. Among patients receiving Pembrolizumab, the overall incidence of all-grade thyroid dysfunction was 19.8% (95% CI: 16.6-23.3%). Pembrolizumab was associated with a significantly increased risk of thyroid dysfunction of all grades, with a relative risk of 3.9 (95% CI: 2.08-7.42%, p= 0.084) in comparison with the controls. Therefore, there is a significant increase in developing thyroid dysfunction in advanced or metastatic NSCLC patients treated with Pembrolizumab.
Highlights
BackgroundLung cancer is the leading cause of cancer-related death all over the world
Programmed cell death 1 (PD-1) is a negative co-stimulatory receptor that is primarily expressed on the surface of activated T-cells, which blocks killing a cell when it interacts with its ligand called programmed cell death ligand (PD-L1) [2,3]
Given the widespread use of Pembrolizumab in advanced or metastatic non-small cell lung cancer (NSCLC) and increasing reports of thyroid dysfunction in patients treated with Pembrolizumab, we have conducted a systematic review of the literature and a meta-analysis of randomized controlled trials to evaluate the incidence and relative risk of thyroid dysfunction in patients with advanced NSCLC treated with Pembrolizumab versus controls
Summary
BackgroundLung cancer is the leading cause of cancer-related death all over the world. Programmed cell death 1 (PD-1) is one of these checkpoints. PD-1 is a negative co-stimulatory receptor that is primarily expressed on the surface of activated T-cells, which blocks killing a cell when it interacts with its ligand called programmed cell death ligand (PD-L1) [2,3]. Some tumors evade the immune response by expressing these ligands on their cell surface [4]. Pembrolizumab is a monoclonal antibody directed against programmed cell death-1 receptor (anti-PD-1) and is used in the adjuvant treatment of non-small cell lung cancer (NSCLC) [5]. As Pembrolizumab acts to block the immune system checkpoints, it can cause T-cells to attack healthy cells, causing various autoimmune diseases referred to as immune-related adverse events (irAEs). Given the widespread use of Pembrolizumab in advanced or metastatic NSCLC and increasing reports of thyroid dysfunction in patients treated with Pembrolizumab, we have conducted a systematic review of the literature and a meta-analysis of randomized controlled trials to evaluate the incidence and relative risk of thyroid dysfunction in patients with advanced NSCLC treated with Pembrolizumab versus controls
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