Afatinib is an oral small-molecule kinase inhibitor (SMKI) approved for treatment of metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) driver mutation. Although oral administration is convenient, most SMKIs experience pH-dependent solubility. A drug-drug interaction between afatinib and proton-pump inhibitors (PPIs) has, however, never been studied in humans.
View Article and Find Full Text PDFAim: With increasing use of immune checkpoint inhibitors (ICIs) more patients will develop severe and potentially life-threatening immune-related adverse events (irAEs). So far, predictive models for the occurrence of grade ≥3 irAEs are lacking. Therefore, we analysed associations between patient and disease characteristics, and the occurrence of grade ≥3 irAEs.
View Article and Find Full Text PDFDue to activation of fibroblast into cancer-associated fibroblasts, there is often an increased deposition of extracellular matrix and fibrillar collagens, e.g. type III collagen, in the tumor microenvironment (TME) that leads to tumor fibrosis (desmoplasia).
View Article and Find Full Text PDFBackground: Dosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I-III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.
Methods: Advanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations.
Background: It is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non-small-cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second-line nivolumab.
Methods: All patients with stage IV NSCLC, who were treated with second-line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated.