Normalization of bone markers and improved survival during zoledronic acid therapy

Abstract

9013 Background: In patients (pts) with bone metastases, elevated N-telopeptide of type I collagen (NTX) levels correlate with increased relative risks (RR) of skeletal-related events (SREs), disease progression, and death (Brown et al. J Natl Cancer Inst. 2005;97:59–69; Coleman et al. J Clin Oncol. 2005;23:4925–4935). Therefore, we conducted an exploratory analysis of 3 large, randomized, controlled trials to investigate whether reductions in NTX levels by treatment with zoledronic acid (ZOL) correspond with decreased risks of SREs and death. Methods: Urinary NTX was measured at baseline and at 3 months in pts with bone metastases from breast (BC; n = 379), prostate (PC; n = 314), or lung cancer and other solid tumors (LC/OST; n = 204) who received ZOL for up to 24 months. Pts were stratified by baseline NTX levels (normal, < 64 nmol/mmol creatinine; elevated, = 64 nmol/mmol creatinine). Results: Approximately 50% of pts had elevated baseline NTX, and NTX normalization occurred within 3 months of ZOL treatment in 81% of pts with BC or LC/OST and in 70% of PC pts. For all tumor types, NTX normalization in response to ZOL correlated with reduced risk of first SRE and death compared with pts whose NTX did not normalize ( Table ). Further analyses using NTX level as a continuous variable revealed that, for all tumor types, any reduction in NTX levels correlated with lower risk of first SRE and death regardless of baseline NTX level. Conclusions: Pts whose NTX normalized on ZOL at 3 months had a lower risk of first SRE and death compared with pts whose elevated baseline NTX did not normalize. Regardless of baseline NTX level, a reduction in NTX over 3 months (absolute and % change) provided a continuum of SRE risk reduction and survival benefit. No significant financial relationships to disclose. [Table: see text]