A randomized, double-blind, multicenter phase 2 trial of denosumab in combination with chemotherapy as first-line treatment of metastatic non-small cell lung cancer.
Journal of Clinical Oncology(2017)
摘要
TPS8130 Background: Non-Small Cell Lung Cancer (NSCLC) is a heterogeneous disease forwhich patients (pts) may benefit from targeted therapies. RANK ligand (RANKL) and its receptor RANK are expressed in a subset of NSCLC tumors (Branstetter, 2013). Results from preclinical models show that RANKL acts directly on RANK-expressing tumor cells to promote tumor progression and metastases (Gonzalez-Suarez, 2010; Tan, 2011). Denosumab is a fully human monoclonal antibody that binds RANKL, approved for the prevention of skeletal-related events in pts with solid tumors and bone metastases. In a study of pts with solid tumors receiving standard treatment, post hoc analysis of those with stage IV NSCLC (n = 702) showed that pts who received denosumab had improved median overall survival (OS) vs those who received zoledronic acid (ZA; HR [95% CI] 0.78 [0.65–0.94], p = 0.01; Scagliotti, 2012). The current trial will correlate tumor RANK and RANKL expression and OS in pts with metastatic NSCLC receiving denosumab in com...
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