Suppression of bone turnover markers by zoledronic acid and correlation with clinical outcome

Abstract

532 The bone resorption marker N-telopeptide (Ntx) provides valuable prognostic information in patients with bone metastases. Across all tumor types an elevated baseline Ntx increases the relative risk of skeletal-related events (SREs), disease progression and death (Brown, et al., ASCO 2003). In this study, urinary N-telopeptide was measured at baseline and at month 3 in 290 patients with breast cancer and multiple myeloma treated with monthly 4 mg of zoledronic acid. At baseline, 120 patients had a urinary Ntx value of 0–64 nmol/mmol creatinine (upper limit of normal for premenopausal women) and 170 had an elevated baseline Ntx (greater than 64 nmol/mmol creatinine). At month 3 of zoledronic acid treatment, only 2/120 (1.7%) patients who started with normal Ntx developed an elevated value. At month 3, 137/170 (80.6%) of patients who began treatment with elevated Ntx had a normal Ntx, 26/170 (15.3%) had persistent elevation of Ntx, and 7/170 (4.1%) patients died. A persistently elevated Ntx (greater than 64 nmol/mmol creatinine) was a significant predictor of subsequently developing a first SRE (RR = 1.71; p = 0.035) and SRE-free survival (RR = 1.65; p = 0.039). It did not predict time to progression of cancer in the skeleton (RR = 1.26; p = 0.417) or survival (RR = 1.33, p = 0.316). In summary, in breast cancer and multiple myeloma patients, normalization of an elevated baseline urinary Ntx at month 3 of treatment with zoledronic acid is a significant predictor of favorable outcome as measured by SREs and time to first SRE. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis Novartis Novartis