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Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab
Arnold, D. (Instituto CUF de Oncologia (I.C.O.), Lisboa)
Fuchs, C. S. (Internal Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA)
Tabernero, Josep (Universitat Autònoma de Barcelona)
Ohtsu, A. (Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan)
Zhu, A. X (Massachusetts General Hospital (Boston))
Garon, E. B. (Hematology Oncology, David Geffen School of Medicine at UCLA Translational Research in Oncology-US Network, Santa Monica, USA)
Mackey, J. R. (Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Canada)
Paz Ares, L. (Hospital Universitario 12 de Octubre (Madrid))
Baron, A. D. (Division of Hematology Oncology, California Pacific Medical Center, San Francisco, USA)
Okusaka, T. (Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan)
Yoshino, Takayuki (Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan)
Yoon, H. H. (Division of Medical Oncology, Mayo Clinic, Rochester, USA)
Das, M. (Oncology, Eli Lilly and Company, Indianapolis, USA)
Ferry, David (Oncology, Eli Lilly and Company, Bridgewater, USA)
Zhang, Y (Oncology, Eli Lilly and Company, Bridgewater, USA)
Lin, Y (Oncology, Eli Lilly and Company, Indianapolis, USA)
Binder, P. (Oncology, Eli Lilly and Company, Bridgewater, USA)
Sashegyi, A.. (Oncology, Eli Lilly and Company, Indianapolis, USA)
Chau, Ian (Department of Medicine, Royal Marsden Hospital, Sutton, UK)

Date: 2017
Abstract: Ramucirumab, the human immunoglobulin G1 monoclonal antibody receptor antagonist of vascular endothelial growth factor receptor 2, has been approved for treating gastric/gastroesophageal junction, non-small-cell lung, and metastatic colorectal cancers. With the completion of six global, randomized, double-blind, placebo-controlled, phase III trials across multiple tumor types, an opportunity now exists to further establish the safety parameters of ramucirumab across a large patient population. An individual patient meta-analysis across the six completed phase III trials was conducted and the relative risk (RR) and associated 95% confidence intervals (CIs) were derived using fixed-effects or mixed-effects models for all-grade and high-grade adverse events (AEs) possibly related to vascular endothelial growth factor pathway inhibition. The number needed to harm was also calculable due to the placebo-controlled nature of all six registration standard trials. A total of 4996 treated patients (N = 2748 in the ramucirumab arm and N = 2248 in the control, placebo arm) were included in this meta-analysis. Arterial thromboembolic events [ATE; all-grade, RR: 0. 8, 95% CI 0. 5-1. 3; high-grade (grade ≥3), RR: 0. 9, 95% CI 0. 5-1. 7], venous thromboembolic events (VTE; all-grade, RR: 0. 7, 95% CI 0. 5-1. 1; high-grade, RR: 0. 7, 95% CI 0. 4-1. 2), high-grade bleeding (RR: 1. 1, 95% CI 0. 8-1. 5), and high-grade gastrointestinal (GI) bleeding (RR: 1. 1, 95% CI 0. 7-1. 7) did not demonstrate a definite increased risk with ramucirumab. A higher percentage of hypertension, proteinuria, low-grade (grade 1-2) bleeding, GI perforation, infusion-related reaction, and wound-healing complications were observed in the ramucirumab arm compared with the control arm. Ramucirumab may be distinct among antiangiogenic agents in terms of ATE, VTE, high-grade bleeding, or high-grade GI bleeding by showing no clear evidence for an increased risk of these AEs in this meta-analysis of a large and diverse patient population. Ramucirumab is consistent with other angiogenic inhibitors in the risk of developing certain AEs. Clinical Trial Numbers: NCT00917384 (REGARD), NCT01170663 (RAINBOW), NCT01168973 (REVEL), NCT01183780 (RAISE), NCT01140347 (REACH), and NCT00703326 (ROSE).
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: VEGF ; VEGFR ; Ramucirumab ; Antiangiogenic ; Adverse events ; Meta-analysis
Published in: Annals of oncology, Vol. 28 (september 2017) , p. 2932-2942, ISSN 1569-8041

DOI: 10.1093/annonc/mdx514
PMID: 28950290


11 p, 388.8 KB

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 Record created 2018-03-26, last modified 2023-03-20



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