Bone turnover marker (BTM) levels and clinical outcomes in advanced cancer patients (pts) treated with antiresorptive bone therapies.

e22236 Background: Advanced cancer pts with metastatic bone disease typically have elevated BTM levels. Antiresorptive agents such as denosumab (DMAB) and zoledronic acid (ZA) can significantly reduce BTM levels. We evaluated BTM levels after treatment with these agents in advanced cancer pts with bone metastases. Methods: This post hoc analysis represents patient-level data from 3 identically designed, blinded, phase 3 trials with pts randomized to receive DMAB (120 mg SC) or ZA (4 mg IV, adjusted for creatinine clearance). The BTMs urinary N-telopeptide (uNTx) and bone-specific alkaline phosphatase (BSAP) were measured at study entry and 3 months. Disease progression (DP), overall survival (OS), and DP in the bone (DPB) were compared in pts with BTMs above and below median levels at month 3 by covariate analyses stratified by treatment and stratification factors based on month 3 assessments. Results: Pts with uNTx levels ≥ the median level of 10.04 nmol/mmol at month 3 had a significantly greater risk of DP (31%) and reduced OS (85%) than pts with uNTx levels < median (Table). Pts with BSAP levels ≥ the median level of 12.56 ng/mL at month 3 had an increased risk for DP (71%) and reduced OS (144%) compared with those who had BSAP levels < median. Pts with uNTx or BSAP levels ≥ the median at month 3 had an increased risk of DPB (11% for uNTX and 27% for BSAP). Conclusions: Pts with BTM levels ≥ median at month 3 of therapy had significantly worse clinical outcomes than pts whose BTM levels were < median. Assessment of BTM levels after antiresorptive therapy may add to identification of pts most at risk for DP and decreased OS. Clinical trial information: NCT00321464, NCT00321620, NCT00330759.Month 3* covariate analysis results: risk of decreased OS or increased DP or DPB. Hazard Ratio (95% Confidence Interval) P-value Decrease in OS uNTXa 1.845 (1.672, 2.036) <0.0001 BSAPb 2.443 (2.200, 2.712) <0.0001 Increase in DP uNTXa 1.307 (1.209, 1.412) <0.0001 BSAPb 1.706 (1.574, 1.848) <0.0001 Increase of DPB uNTXa 1.114 (1.005, 1.235) 0.0407 BSAPb 1.270 (1.142, 1.413) <0.0001 *Comparing ≥ median to < median. aMedian uNTx levels = 10.04 nmol/mmol. uNTx ≥ median, n=2150; uNTx < median, n=2149. bMedian BSAP level = 12.56 ng/mL. BSAP ≥ median, n=2157; BSAP < median, n=2159.