@article{f4c638af17dd4c5eac83d240d96a5067,
title = "Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features - An exploratory analysis of placebo-controlled trials",
abstract = "Background: Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials. Patients and methods: Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models. Results: Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX (Z100 nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease. Conclusion: These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD.",
author = "Coleman, {Robert E.} and Allan Lipton and Luis Costa and Cook, {Richard J.} and Lee, {Ker Ai} and Fred Saad and Brown, {Janet E.} and Evangelos Terpos and Major, {Pierre P.} and Norio Kohno and Matthew Smith and Body, {Jean Jacques}",
note = "Funding Information: This work was supported by Novartis Pharmaceuticals Corporation. As the sponsor of the studies included in the meta-analysis, Novartis made the data available to the authors. All analyses were conducted by the independent statistician (RJC). The corresponding author initiated and directed all analyses, had access to all data in the study, and took final responsibility for the decision to submit for publication. All authors were responsible for the content of this review. Funding Information: REC has served as a consultant/advisor to Novartis, and has previously given expert testimony on behalf of Novartis. AL has participated as a consultant for Amgen, Novartis, Acceleron Pharmaceuticals, Monogram Biosciences, and GlaxoSmithKline; received honoraria from Amgen, Pfizer, Acceleron Pharmaceuticals, GlaxoSmithKline, and Novartis; received research funding from Novartis, Monogram Biosciences, and Oncogene Science; and has given expert testimony for Novartis. LC has received honoraria from Novartis and Amgen, and speaker fees from Novartis. RJC has received honoraria and consulting fees from Abbott, Amgen, GlaxoSmithKline, and Novartis. FS has received research funding, attended advisory board meetings, and received honoraria for speaking on behalf of Novartis. JEB has received a travel grant and honoraria from Novartis; she has also received a travel grant, honoraria, research funding, and speaker fees from Amgen, and has participated in advisory boards for Bristol-Myers Squibb. ET has received honoraria and research funding from Novartis and Janssen-Cilag, and has participated in advisory boards and served on steering committees for Amgen. PPM has received consultancy fees from Novartis for participating in advisory boards and FDA meetings. NK has received honoraria from Pfizer and Novartis. JJB has received consultancy fees and speaker fees from Novartis and Amgen. MS reports no disclosures relevant to this manuscript. KAI reports no conflicts of interest. ",
year = "2013",
month = jun,
doi = "10.1016/j.jbo.2013.01.002",
language = "English (US)",
volume = "2",
pages = "70--76",
journal = "Journal of Bone Oncology",
issn = "2212-1374",
publisher = "Elsevier GmbH",
number = "2",
}