A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC : the European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR trial

Introduction Receptor activator of NF-kB ligand stimulates NF-kB–dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. Methods Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3–4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. Results A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6–11.0) months in the control arm versus 8.2 (7.5–10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78–1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77–1.35), whereas for those without, HR was 0.90 (95% CI: 0.66–1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. Conclusions Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases

Diagnostic bronchoscopy: state of the art

Since the introduction of the flexible fibreoptic bronchoscope in the late 1960s there have been relatively few technological advances for three decades, aside from the development of a white light video bronchoscope with a miniature charge-coupled device built in its tip replacing the fibreoptics. White light flexible videobronchoscopy with its ancillary devices (forceps biopsy, bronchial brushing, bronchoalveolar lavage, bronchial washings and transbronchial needle aspiration) has long been the only established diagnostic bronchoscopic technique. With the advances in microtechnology over the past two decades, recent technical developments such as autofluorescence bronchoscopy and endoscopic ultrasound allow better evaluation of endobronchial, mediastinal and parenchymal lesions

Endosonography for lung cancer staging: predictors for false-negative outcomes

Development and application of statistical models for medical scientific researc

Systematic and combined endosonographic staging of lung cancer (SCORE study)

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COST-EFFECTIVENESS AND QUALITY OF LIFE RESULTS FROM THE ASTER STUDY: ENDOBRONCHIAL AND ENDOSCOPIC ULTRASOUND VS SURGICAL STAGING IN POTENTIALLY RESECTABLE LUNG CANCER

Pathogenesis and treatment of chronic pulmonary disease

A RANDOMISED CONTROLLED TRIAL COMPARING COMBINED EBUS/EUS FOLLOWED BY SURGICAL STAGING VERSUS SURGICAL STAGING ALONE IN NON-SMALL CELL LUNG CANCER: THE ASTER STUDY

Diabetes mellitus: pathophysiological changes and therap