Impact of denosumab use on the survival of untreated non-squamous non-small cell lung cancer patients with bone metastases
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.
Keywords
Non-small cell lung cancer Bone metastases Denosumab Survival ChemotherapyNotes
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interests to disclose.
Ethical approval
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.
Informed consent
Informed consent, as general consent, was obtained from all individual participants included in the study.
Funding
We had no research fund for this study.
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 PubMedPubMedCentralGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350:1655–1664. doi: 10.1056/NEJMra030831 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30. doi: 10.3322/caac.21166 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefGoogle Scholar