Survival benefits of zoledronic acid in patients with bone metastases from non-small cell lung cancer and high NTX levels: The role of BALP

Abstract

19003 Background: In a clinical trial of zoledronic acid (ZOL) vs placebo in patients (pts) with bone metastases from solid tumors (not breast or prostate cancer; N = 773), ∼50% of pts had non-small cell lung cancer (NSCLC). Among all pts and NSCLC pts, ∼50% had high baseline levels of biochemical markers of bone resorption (N-telopeptide of type I collagen [NTX] ≥ 64 nmol/mmol creatinine) or formation (bone-specific alkaline phosphatase [BALP] ≥ 146 IU/L). Besides skeletal complication prevention, ZOL significantly prolonged survival in NSCLC pts with high baseline NTX, even after adjustment for other significant covariates (Hirsh V, et al. J Thorac Oncol. In press). However, the report did not include analyses by baseline BALP levels. Methods: Pts with NSCLC and bone marker data were included (n = 382), and analyses were performed by baseline NTX and BALP status. Kaplan-Meier survival estimates and Cox regression analyses of treatment by covariate interactions were performed. Results: In univariate analyses, variables associated with poorer survival were high pain score (P = .002), male sex (P = .020), low FACT-G score (P < .001), narcotic analgesics (P = .003), ECOG performance status > 1 (P < .001), high NTX (P = .003), high BALP (P = .020), creatinine ≥ 1.0 mg/dL (P = .032), and LDH ≥ 247 U/L (P = .005). In a multivariate model of treatment and baseline NTX and BALP, ZOL was associated with significantly increased survival vs placebo in the high-NTX subset (P = .02), but not in the high-BALP subset (P = .40). However, significant heterogeneity of benefits was detected between high- and low-BALP pts in the high-NTX subset (P = .04). Therefore, each group was assessed separately in Kaplan-Meier analyses. In the high-NTX subset, ZOL was associated with a 46% reduced risk of death in high-BALP pts (P = .006 vs placebo), but had no association with survival in low-BALP pts. ZOL was not significantly associated with survival in pts with low baseline NTX regardless of BALP status. Conclusions: Although prospective analyses are needed to elucidate the role of NTX and BALP, this analysis suggests that ZOL may prolong survival in a subset of NSCLC pts with advanced bone disease and high baseline levels of both markers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Oncology, GTx Inc., Merck, Novartis Oncology, Novartis Pharmaceuticals Inc. Novartis Oncology, Novartis Pharmaceuticals, Inc. Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc. - Speakers Bureau