| Author/Editor | Peters, Solange; Danson, Sarah; Hasan, Baktiar; Dafni, Urania; Reinmuth, Niels; Majem, Margarita; Tournoy, Kurt G.; Mark, Michael T.; Pless, Miklos; Cobo, Manuel; Mohorčič, Katja | |
| Title | A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC | |
| Type | članek | |
| Vol. and No. | Letnik 15, št. 10 | |
| Publication year | 2020 | |
| Volume | str. 1647-1656 | |
| ISSN | 1556-1380 - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | |
| Language | eng | |
| Abstract | 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. | |
| Descriptors | Carcinoma, non-small cell lung Neoplasms Neoplasm metastases Nedrobnocelični karcinom pljuč Novotvorbe Metastaze novotvorb | |
| Keywords | rak kostni zasevki denosumab cancer bone metastases denosumab |