%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://ndownloader.figshare.com/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