(ChemotherapyAdvisor) – Denosumab significantly improves overall survival when compared with zoledronic acid in patients with lung cancer and bone metastases, according to results of an exploratory analysis of a Phase 3 randomized study of the agents for preventing skeletal-related events presented at the 3rd European Lung Cancer Conference in Geneva, Switzerland, April 18–21.
Denosumab (XGEVA) is a fully human RANKL antibody approved to prevent skeletal-related events in patients with solid tumors and bone metastasis. The multinational Phase 3 study randomly assigned patients with bone metastases from solid tumors (except breast and prostate) or with multiple myeloma to either a monthly subcutaneous denosumab injection 120mg or intravenous zoledronic acid 4mg (dose adjusted for renal function). Daily calcium and vitamin D supplements were recommended.
In this analysis, overall survival was assessed among 811 patients with lung cancer enrolled in the study, 702 with non–small-cell lung cancer (NSCLC) and 109 with small cell lung cancer (SCLC), who received either denosumab or zoledronic acid. Mean age was 61 years; most patients were male (71%) and Caucasian (88%) and had an Eastern Cooperative Oncology Group performance status of 0 or 1 (85% for denosumab and 80% for zoledronic acid). The majority of patients (89%) in each treatment group had received prior chemotherapy.
Scagliotti et al. found that overall survival was prolonged with denosumab over zoledronic acid for all patients with lung cancer: median survival was 8.9 months vs. 7.7 months (HR 0.80; P=0.01), as well as for the subgroups with NSCLC (9.5 months vs. 8.1 months, HR 0.78; P=0.01) and SCLC (7.6 months vs. 5.1 months, HR 0.81; P=0.36). The difference in overall survival observed between the two groups was not affected by prior chemotherapy or difference in ECOG status, they reported.
For patients with squamous cell carcinoma (n=163), median overall survival was 8.6 months for denosumab and 6.4 months for zoledronic acid (HR 0.68; P=0.035) and, for adenocarcinoma, 9.6 months vs. 8.2 months, respectively (HR 0.80; P=0.075).
A total of 96.8% of patients reported adverse events (AEs) with denosumab and 95.4% with zoledronic acid. Serious AEs occurred in 66.0% of patients in the denosumab group and 72.9% in the zoledronic acid arm; osteonecrosis of the jaw occurred in 0.7% and 0.8% of the denosumab and zoledronic arms, respectively. Adverse event rates for hypocalcemia were 8.6% for denosumab and 3.8% for zoledronic acid.