Publication
Title
RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ) : non bis in idem?
Author
Abstract
Purpose The purpose of this study was to assess the necessity of post-marketing safety monitoring focused on osteonecrosis of the jaw (ONJ) in patients with bone metastatic cancer treated with denosumab (AMG162). Methods The ONJ safety data from three randomized phase III trials were pooled, and risk ratios and power were computed using traditional methods and simulation. Results A total of 89 ONJ cases (1.57%; 95% CI, 1.261.92) were reported with 52 (1.83%; 95% CI, 1.372.39) occurring in the denosumab group (n = 2,841) and 37 (1.30%; 95% CI, 0.921.79) in the zoledronic acid group (n = 2,836). Overall, the pooled risk ratio (RR) for ONJ was 1.40 (95% CI, 0.922.13; p = 0.11). In the trials reporting superior therapeutic efficacy of denosumab, the RR for ONJ was 1.61 (95% CI, 0.992.62; p = 0.052). However, neither separately nor pooled had any trial adequate power (>80%) to detect excess relative risks of ONJ of up to 76%, assuming fixed ONJ rates in the control arms. The joint power of the trials to detect the observed excess relative risk of 40% was only 36%. The rate of mucosal healing in patients with ONJ appeared similar in both groups (RR, 1.28; 95% CI, 0.662.45; p = 0.5). Conclusions Although the overall frequency of ONJ was low, post-marketing riskbenefit studies with this novel compound appear warranted focusing specifically on this rare toxicity, which can potentially have a high impact on quality of life.
Language
English
Source (journal)
Supportive care in cancer. - Berlin
Publication
Berlin : 2011
ISSN
0941-4355
Volume/pages
19:12(2011), p. 2035-2040
ISI
000296362900019
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 06.01.2012
Last edited 31.05.2017
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