Abstract P3-07-45: Bone turnover marker levels and clinical outcomes in patients with breast cancer and bone metastases treated with bone antiresorptive therapies
Authors: Lipton A , Stopeck A , Body J-J , Von Moos R , De Boer R , Paiva Gadelha Guimaraes A , Tonkin K , Fujiwara Y , Zhu L , Warner D 
Published: May 2016

Abstract
INTRODUCTION AND OBJECTIVES: Patients with advanced breast cancer (BC) and metastatic bone disease typically have elevated serum levels of bone turnover markers (BTMs). Potent antiresorptive agents, such as denosumab and zoledronic acid, can significantly reduce BTM levels (Stopeck et al. J Clin Oncol 2010). Prior studies have provided evidence that higher BTM baseline levels may be associated with worse clinical outcomes (Ali et al. Ann Oncol 2004). In this analysis, we assessed the association between BTM levels after treatment with antiresorptive agents and overall survival (OS), disease progression (DP) and disease progression in the bone (DPB) in patients with advanced BC and bone metastases.
METHODS: This post-hoc analysis included data from patients with BC and bone metastases enrolled in an international, blinded phase 3 trial who were randomized to receive either denosumab (120 mg SC) or zoledronic acid (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 at study month 3. The clinical outcomes of OS, DP, and DPB were compared in patients with BTMs above or below median levels at month 3 of antiresorptive therapy. These covariate analyses were based on Cox models stratified by treatment, prior SRE before month 3, prior bisphosphonate use, chemotherapy at randomization, and region (Japan or other countries).
RESULTS: A total of 1705 patients were measured for uNTx serum levels, with 895 patients ≥ and 810 &lt; the median of 10.40 nmol/mmol at month 3. Similarly, BSAP levels were measured in a total of 1708 patients, with 855 patients ≥ and 853 &lt; the median BSAP level of 10.89 ng/mL at month 3. Patients with uNTx levels ≥ the median at month 3 had a significantly reduced OS (by 54%) and a greater risk of both DP (by 21%) and DPB (by 23%) than patients with uNTx levels &lt; median (see Table). Similarly, patients with BSAP levels ≥ the median level at month 3 had an increased risk for reduced OS (by 197%), DP (by 67%) and DPB (by 56%) compared with patients whose BSAP levels &lt; median. After adjusting for risk factors suggestive of more advanced disease such as visceral metastases or &gt; 2 bone metastases, the correlation between elevated BTMs and reduced OS and greater risk of DP and DPB was maintained.
CONCLUSIONS: Patients with BTM levels ≥ median at month 3 of antiresorptive therapy had generally worse clinical outcomes than patients whose BTM levels were &lt; median. Assessment of uNTx and BSAP serum levels after treatment with antiresorptive therapy can add to our understanding of which patients with breast cancer and bone metastases are most at risk for decreased OS, or increased DP or DPB.
Month 3*Covariate Analysis Results: Risk of Decreased OS or Increased DP or DPBClinical OutcomeHazard Ratio (95% Confidence Interval)P-valueDecrease in OSuNTXa1.539 (1.270, 1.866)&lt;0.0001BSAPb2.966 (2.422, 3.633)&lt;0.0001Increase in DPuNTXa1.214 (1.071, 1.377)=0.0024BSAPb1.666 (1.470, 1.888)&lt;0.0001Increase of DPBuNTXa1.231 (1.054, 1.437)=0.0087BSAPb1.563 (1.342, 1.821)&lt;0.0001*Comparing ≥ median to &lt; median. aMedian uNTx levels=10.40 nmol/mmol. bMedian BSAP level=10.89 ng/mL.
Citation Format: Lipton A, Stopeck A, Body J-J, Von Moos R, De Boer R, Paiva Gadelha Guimaraes A, Tonkin K, Fujiwara Y, Zhu L, Warner D. Bone turnover marker levels and clinical outcomes in patients with breast cancer and bone metastases treated with bone antiresorptive therapies. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-45.