%0 Generic
%A S., Noguchi
%A N., Shinohara
%A T., Ito
%A A., Ohtsu
%A A., Ravaud
%A G., Jerusalem
%A N., Ohno
%A J., Gallo
%A E., Bouillaud
%A J, Fan
%A N., Nonomura
%D 2017
%T Supplementary Material for: Relationship between Pulmonary Adverse Events and Everolimus Exposure in Japanese and Non-Japanese Patients: A Meta-Analysis of Oncology Trials
%U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Relationship_between_Pulmonary_Adverse_Events_and_Everolimus_Exposure_in_Japanese_and_Non-Japanese_Patients_A_Meta-Analysis_of_Oncology_Trials/4670494
%R 10.6084/m9.figshare.4670494.v1
%2 https://karger.figshare.com/ndownloader/files/7623775
%K Neoplasm
%K Pharmacokinetics
%K Solid tumor
%K Lung pathology
%X Aims: This meta-analysis explores the relationship between the everolimus minimum (Cmin) and maximum (Cmax) exposure and the risk for pulmonary adverse events (AEs) in Japanese versus non-Japanese patients. Methods: Patient-level data from patients treated with daily everolimus in advanced solid tumor trials were evaluated using a Cox regression model, stratified by cancer type or treatment arm, with log-transformed time-averaged Cmin or Cmax as a time-varying covariate. Kaplan-Meier analysis was used to evaluate the relationship between pulmonary AEs and pharmacokinetic parameters. Results: Thirty studies were identified. In the Cmin population (n = 1,962), all-grade pulmonary AE incidence was significantly higher in Japanese versus non-Japanese patients (19.9 vs. 9.4%). Pharmacokinetic parameters were similar between Japanese and non-Japanese patients. A 2-fold increase in everolimus Cmin significantly increased the risk for the first any-grade pulmonary AE in Japanese (risk ratio: 1.824; 95% CI: 1.141-2.918) and non-Japanese patients (risk ratio: 1.406; 95% CI: 1.156-1.710). Conclusions: The risk for pulmonary AEs is related to everolimus exposure. Local monitoring and reporting differences might account for the significantly higher reported incidence of low-grade everolimus-associated pulmonary AEs in Japanese versus non-Japanese patients. Patients should be carefully monitored for early signs of pulmonary AEs, and appropriate medical management should be implemented.
%I Karger Publishers