Abstract
Purpose
Denosumab reduces the incidence of skeletal-related events (SREs) in solid tumor patients with bone metastases (BM). However, there have been no detailed reports of the efficacy of denosumab in untreated non-squamous non-small cell lung cancer (NSCLC) patients with BM.
Methods
The medical records of patients with untreated non-squamous NSCLC and BM at diagnosis at our institution were reviewed retrospectively. The overall survival (OS) and the time to SREs were analyzed according to the treatment for the BM.
Results
Of the total of 149 patients who were eligible, 52 had received denosumab (Dmab group), 51 had received zoledronic acid (ZA group), and 46 had received no treatment (No-Tx group) for the BM. The frequencies of prior SREs were higher in the Dmab group and ZA group than in the No-Tx group (44, 41 and 22%, respectively); however, there were no significant differences in any of the other clinicopathological characteristics examined among the three groups. The median OS in the Dmab group, ZA group and No-Tx group were 21.4 months, 12.7 months and 10.5 months, respectively; the OS was significantly longer in the Dmab group than in the ZA group (P < 0.01). Results of multivariate analysis revealed that denosumab treatment was significantly associated with a more favorable survival [hazard ratio, 0.500; 95% CI 0.332–0.741; P < 0.01]. No significant difference in the time to SREs was observed among the three groups.
Conclusions
Our results suggest that treatment with denosumab may improve the overall survival of non-squamous NSCLC patients with BM.
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References
Daniele S et al (2015) Natural history of non-small-cell lung cancer with bone metastases. Sci Rep 5:18670 doi:10.1038/srep18670
Eisenhauer EA et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer (Oxford, England: 1990) 45:228–247 doi:10.1016/j.ejca.2008.10.026
Garraway IP (2013) Targeting the RANKL pathway: putting the brakes on prostate cancer progression in bone. J Clin Oncol 31:3838–3840. doi:10.1200/jco.2013.50.1544
Henry DH et al (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132. doi:10.1200/jco.2010.31.3304
Kitazawa S, Kitazawa R (2002) RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol 198:228–236. doi:10.1002/path.1199
Peng X et al (2013) Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PloS One 8:e58361. doi:10.1371/journal.pone.0058361
Riihimaki M, Hemminki A, Fallah M, Thomsen H, Sundquist K, Sundquist J, Hemminki K (2014) Metastatic sites and survival in lung cancer. Lung Cancer 86:78–84 doi:10.1016/j.lungcan.2014.07.020
Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350:1655–1664. doi:10.1056/NEJMra030831
Rosen LS et al (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind placebo-controlled trial. Cancer 100:2613–2621. doi:10.1002/cncr.20308
Scagliotti GV et al (2012) Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 7:1823–1829. doi:10.1097/JTO.0b013e31826aec2b
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30. doi:10.3322/caac.21166
Smith MR et al (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised placebo-controlled trial. Lancet 379:39–46. doi:10.1016/s0140-6736(11)61226-9
Smith MR et al (2013) Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol 31:3800–3806. doi:10.1200/jco.2012.44.6716
Stopeck AT et al (2016) Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer Supportive care in cancer : official journal of the Multinational Association of. Supp Care Cancer 24:447–455. doi:10.1007/s00520-015-2904-5
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Informed consent, as general consent, was obtained from all individual participants included in the study.
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Udagawa, H., Niho, S., Kirita, K. et al. Impact of denosumab use on the survival of untreated non-squamous non-small cell lung cancer patients with bone metastases. J Cancer Res Clin Oncol 143, 1075–1082 (2017). https://doi.org/10.1007/s00432-017-2350-5
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DOI: https://doi.org/10.1007/s00432-017-2350-5