Abstract
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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.