153P - Ramucirumab safety in East Asian (EA) compared to non-EA patients: A meta-analysis of adverse events (AEs) in 6 global, randomized, double-blind, p...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Complications/Toxicities of treatment
Presenter Hyun Cheol Chung
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors H.C. Chung1, Y. Chao2, K. Lee3, M. Kudo4, C. Yen5, T.W. Kim6, K. Yamazaki7, J. Shih8, S. Kim6, J. Sohn1, R. Cheng9, Y. Zhang10, P. Binder10, G. Mi11, M. Orlando12, K. Muro13
  • 1Medical Oncology, Yonsei Cancer Center, 120-752 - Seoul/KR
  • 2Oncology, National Yang-Ming University and Taipei Veterans General Hospital, 112 - Taipei/TW
  • 3Oncology, Seoul National University Bundang Hospital, 463-707 - Seongnam/KR
  • 4Oncology, Kinki University School of Medicine, 3-4-1 - Osaka/JP
  • 5Oncology, National Cheng Kung University Hospital, 704 - Tainan/TW
  • 6Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 5505 - Seoul/KR
  • 7Oncology, Shizuoka Cancer Center, 1007 - Shizuoka/JP
  • 8Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 9Medical, Eli Lilly and Company, 105 - Taipei/TW
  • 10Medical, Eli Lilly and Company, 08807 - Bridgewater/US
  • 11Statistics - Oncology, Eli Lilly and Company, 46225 - Indianapolis/US
  • 12Medical, Eli Lilly and Company, 1430 - Buenos Aires/AR
  • 13Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP

Abstract

Background

Ethnicity may account for differences in pharmacokinetics or pharmacodynamics of drugs, leading to variability in drug response and tolerance. A meta-analysis was conducted to examine the incidence of AEs possibly associated with ramucirumab in EA compared to non-EA patients.

Methods

Six global, randomized, double-blind, phase 3 registration trials investigating ramucirumab were assessed. Relative risk (RR) and 95% confidence intervals (CIs) were calculated for all-grade and grade ≥3 AEs using fixed-effects and mixed-effects models or pooled rate of events across trials, depending on heterogeneity of the trials and observation of rare AEs.

Results

4996 randomized patients received ramucirumab or placebo; 802 (16%) were EA (ramucirumab [N = 411] and placebo [N = 391]) and 4194 were non-EA (ramucirumab [N = 2337] and placebo [N = 1857]). In general, the patient baseline characteristics were balanced between treatment arms in EA and non-EA patients. Incidence rates and RR of AEs are presented in the Table. Grade ≥3 AEs possibly associated with ramucirumab occurring in ≥ 5% of both EA and non-EA patients were neutropenia (42.1% vs. 25.5%), hypertension (8.8% vs. 9.0%), and febrile neutropenia (6.1% vs. 7.0%). The ramucirumab incidence rates of all-grade proteinuria, bleeding, and neutropenia, and grade ≥3 neutropenia, were ≥5% higher in EA compared to non-EA patients.

Conclusions

Despite differences in incidence rates of some AEs between EA and non-EA patients, in particular grade ≥3 neutropenia, there was no substantial difference between EA and non-EA patients in RR for AEs possibly associated with ramucirumab in these phase 3 trials.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

Eli Lilly and Company

Disclosure

H.C. Chung: Grants/Research Support from Lilly, GSK, Speakers Bureau/Honoraria from Merck-Serono, Lilly and Consulting Fees from Taiho, Celltrion, MSD, Lilly, Quintiles, BMS. M. Kudo: Lecturer: Bayer, Kowa, Taiho Grants: Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai. T.W. Kim: Grant: Roche, Bayer Honoraria: Amgen. K. Yamazaki: Speakers Bureau: Takeda, Chugai, Eli Lilly, Taiho, Yakult, Daiichi Sankyo, Merck Serono. J-Y. Shih: Speaking honoraria from AstraZeneca, Roche, Pfizer, Boehringer Ingelheim and Eli Lilly. R. Cheng, Y. Zhang, P. Binder: Full-time employee of Eli Lilly and Company. G. Mi, M. Orlando: Full-time employee of Eli Lilly and Company and stock ownership in Eli Lilly and Company. All other authors have declared no conflicts of interest.