Skeletal-related events (SREs), including fractures, spinal cord compression, hypercalcemia and/or the need for surgery or radiation to bone, do represent serious complications and also major morbidities, sometimes fatal, in non-small-cell lung cancer (NSCLC) patients. Indeed, SREs negatively impact quality of life.
Zoledronic acid (ZA) was shown to be useful in this scenario: in comparison to placebo, 4-mg ZA was found to reduce the risk of developing a SRE (HR 0.693, p 0.003) (Rosen et al. Cancer 100:2613, 2004), and it has been used in the daily clinical practice. More recently, the fully human monoclonal antibody denosumab (Dmab), directed to receptor activator of nuclear factor kappa-B ligand (RANK-L) was compared to ZA in a prospective, double-blind, double-dummy, non-inferiority clinical trial, in which Dmab 120 mg or ZA 4 mg were administered to 1779 patients diagnosed with advanced solid tumours (excluding prostate and breast cancer) and bone metastasis, or multiple myeloma. Supplemental oral calcium and vitamin D were recommended.
Overall, Dmab was non inferior to ZA in delaying time to first on-study SRE (HR 0.84, p 0.0007) (Henry et al. J Clin Oncol 29:1125, 2011).
More recently, in a post hoc analysis on survival among 811 patients diagnosed with metastatic lung cancer (either NSCLC or SCLC), and included in this study, an interesting overall survival advantage was detected among those patients treated with Dmab: 8.9 versus 7.7 months (HR 0.80; 95% CI 0.67-0.95; p 0.01) (Scagliotti et al. 14th World Congress on Lung Cancer, July 2011, Amsterdam, The Netherlands).
In terms of health care decision-making, an analysis by Dranitsaris and Hatzimichael (Supp Care Cancer 20:1353, 2012) was conducted to help us in comparing Dmab (a new intervention) and ZA in terms of the number needed to treat (NNT) in order to avoid one additional patient presenting a SRE in a more clinically meaningful way. In the above mentioned trial published by Henry et al., the binary clinical data analysis detected an absolute risk reduction of 4.9% in developing a SRE, favouring Dmab, which translates in a NNT of 21 patients need to be treated with Dmab for up to 34 months in order to avoid one patient with solid tumours and bone metastasis (excluding breast cancer and prostate cancer), or multiple myeloma, developing a SRE.
As mentioned by the authors, NNTs should not be determined for differences not statistically different, and that is the case for this analysis. However, we must pay attention to these numbers, in conjunction to toxicity profiles and available resources, when deciding which drug (ZA or Dmab) will be prescribed in our NSCLC patients with bone metastasis in order to prevent and delay SREs.
Reference: Dranitsaris G and Hatzimichael E. Interpreting results from oncology clinical trials: a comparison of denosumab to zoledronic acid for the prevention of skeletal-related events in cancer patients. Supp Care Cancer 20:1353-60, 2012. DOI: 10.1007/s00520-012-1461-4