Open AccessRamucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials
Author(s) -
Chia Jui Yen,
Kei Muro,
Tae Won Kim,
Masatoshi Kudo,
JinYuan Shih,
Moon Hyoung Lee,
Yee Chao,
Sang We Kim,
Kentaro Yamazaki,
Joohyuk Sohn,
Ruochuan Cheng,
Yawei Zhang,
P. Binder,
Gu Mi,
Mauro Orlando,
Hyun Cheol Chung
Publication year - 2018
Publication title -
journal of global oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.002
H-Index - 17
ISSN - 2378-9506
DOI - 10.1200/jgo.17.00227
Subject(s) - ramucirumab , medicine , placebo , adverse effect , relative risk , randomized controlled trial , gastroenterology , confidence interval , chemotherapy , pathology , alternative medicine
Purpose Several ramucirumab trials have reported a higher incidence of selected adverse events (AEs) in East Asian (EA) patients with cancer versus non-EA patients. A meta-analysis was conducted across six completed phase III trials to establish the safety parameters of ramucirumab in EA compared with non-EA patients. Materials and Methods Six global, randomized, double-blind, placebo-controlled, phase III registration trials investigating ramucirumab were assessed. Relative risks (RRs) and 95% CIs were calculated for selected all-grade and grade ≥ 3 AEs using fixed-effects and mixed-effects models. Ratio of RR and number needed to harm were calculated for AEs (all grade and grade ≥ 3) between EA and non-EA patients. Results Of 4,996 randomly assigned patients receiving ramucirumab or placebo, 802 (16.1%) were EA (ramucirumab, n = 411; placebo, n = 391) and 4,194 were non-EA (ramucirumab, n = 2,337; placebo, n = 1,857). Patient baseline characteristics were generally balanced between treatment arms in EA and non-EA patients, excluding sex and body weight. Grade ≥ 3 AEs possibly associated with ramucirumab, which were increased in EA versus non-EA patients, included neutropenia (42.1% v 25.5%, respectively) and proteinuria (3.9% v 0.6%, respectively). There was an increase in the RR of several grade ≥ 3 AEs, including hypertension and proteinuria, in ramucirumab-treated EA and non-EA patients compared with placebo. The ratio of RR revealed no significant differences between EA and non-EA patients for all-grade and grade ≥ 3 AEs. Conclusion Despite the enhanced propensity of selected AEs in EA patients relative to non-EA patients, there were no substantial differences in the RR for AEs possibly associated with ramucirumab in these phase III trials.