Ramucirumab safety in East Asian patients

A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials

Chia Jui Yen, Kei Muro, Tae Won Kim, Masatoshi Kudo, Jin Yuan Shih, Keun Wook Lee, Yee Chao, Sang We Kim, Kentaro Yamazaki, Joo Hyuk Sohn, Rebecca Cheng, Yawei Zhang, Polina Binder, Gu Mi, Mauro Orlando, Hyuncheol Chung

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
JournalJournal of Global Oncology
Volume2018
Issue number4
DOIs
Publication statusPublished - 2018 Mar 1

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Phase III Clinical Trials
Meta-Analysis
Placebos
Safety
ramucirumab
Proteinuria

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yen, Chia Jui ; Muro, Kei ; Kim, Tae Won ; Kudo, Masatoshi ; Shih, Jin Yuan ; Lee, Keun Wook ; Chao, Yee ; Kim, Sang We ; Yamazaki, Kentaro ; Sohn, Joo Hyuk ; Cheng, Rebecca ; Zhang, Yawei ; Binder, Polina ; Mi, Gu ; Orlando, Mauro ; Chung, Hyuncheol. / Ramucirumab safety in East Asian patients : A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials. In: Journal of Global Oncology. 2018 ; Vol. 2018, No. 4.
@article{00595730986144aca7fbfebeaf9c1f2b,
title = "Ramucirumab safety in East Asian patients: A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials",
abstract = "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.",
author = "Yen, {Chia Jui} and Kei Muro and Kim, {Tae Won} and Masatoshi Kudo and Shih, {Jin Yuan} and Lee, {Keun Wook} and Yee Chao and Kim, {Sang We} and Kentaro Yamazaki and Sohn, {Joo Hyuk} and Rebecca Cheng and Yawei Zhang and Polina Binder and Gu Mi and Mauro Orlando and Hyuncheol Chung",
year = "2018",
month = "3",
day = "1",
doi = "10.1200/JGO.17.00227",
language = "English",
volume = "2018",
journal = "Journal of global oncology",
issn = "2378-9506",
publisher = "American Society of Clinical Oncology",
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Yen, CJ, Muro, K, Kim, TW, Kudo, M, Shih, JY, Lee, KW, Chao, Y, Kim, SW, Yamazaki, K, Sohn, JH, Cheng, R, Zhang, Y, Binder, P, Mi, G, Orlando, M & Chung, H 2018, 'Ramucirumab safety in East Asian patients: A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials', Journal of Global Oncology, vol. 2018, no. 4. https://doi.org/10.1200/JGO.17.00227

Ramucirumab safety in East Asian patients : A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials. / Yen, Chia Jui; Muro, Kei; Kim, Tae Won; Kudo, Masatoshi; Shih, Jin Yuan; Lee, Keun Wook; Chao, Yee; Kim, Sang We; Yamazaki, Kentaro; Sohn, Joo Hyuk; Cheng, Rebecca; Zhang, Yawei; Binder, Polina; Mi, Gu; Orlando, Mauro; Chung, Hyuncheol.

In: Journal of Global Oncology, Vol. 2018, No. 4, 01.03.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ramucirumab safety in East Asian patients

T2 - A meta-analysis of six global, randomized, double-blind, placebo-controlled, phase III clinical trials

AU - Yen, Chia Jui

AU - Muro, Kei

AU - Kim, Tae Won

AU - Kudo, Masatoshi

AU - Shih, Jin Yuan

AU - Lee, Keun Wook

AU - Chao, Yee

AU - Kim, Sang We

AU - Yamazaki, Kentaro

AU - Sohn, Joo Hyuk

AU - Cheng, Rebecca

AU - Zhang, Yawei

AU - Binder, Polina

AU - Mi, Gu

AU - Orlando, Mauro

AU - Chung, Hyuncheol

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

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U2 - 10.1200/JGO.17.00227

DO - 10.1200/JGO.17.00227

M3 - Article

VL - 2018

JO - Journal of global oncology

JF - Journal of global oncology

SN - 2378-9506

IS - 4

ER -