Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/73799
Título: 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
Autores/as: Peters, Solange
Danson, Sarah
Hasan, Baktiar
Dafni, Urania
Reinmuth, Niels
Majem, Margarita
Tournoy, Kurt G.
Mark, Michael T.
Pless, Miklos
Cobo, Manuel
Rodríguez Abreu, Delvys 
Falchero, Lionel
Moran, Teresa
Ortega Granados, Ana Laura
Monnet, Isabelle
Mohorcic, Katja
Sureda, Bartomeu Massutí
Betticher, Daniel
Demedts, Ingel
Macias, Jose Antionio
Cuffe, Sinead
Luciani, Andrea
Sanchez, Jose Garcia
Curioni-Fontecedro, Alessandra
Gautschi, Oliver
Price, Gillian
Coate, Linda
von Moos, Roger
Zielinski, Christoph
Provencio, Mariano
Menis, Jessica
Ruepp, Barbara
Pochesci, Alessia
Roschitzki-Voser, Heidi
Besse, Benjamin
Rabaglio, Manuela
O'Brien, Mary E.R.
Stahel, Rolf A.
Clasificación UNESCO: 32 Ciencias médicas
Palabras clave: Bone Metastases
Denosumab
NSCLC
RANK
RANKL
Fecha de publicación: 2020
Publicación seriada: Journal of Thoracic Oncology 
Resumen: 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.
URI: http://hdl.handle.net/10553/73799
ISSN: 1556-0864
DOI: 10.1016/j.jtho.2020.06.011
Fuente: Journal of Thoracic Oncology [ISSN 1556-0864], v. 15(10), p. 1647-1656
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