Rash to mTOR inhibitor everolimus: Systematic review and meta-analysis.

Abstract

e19624 Background: Everolimus is an mTOR inhibitor approved for treatment of renal cell carcinoma, subependymal giant cell astrocytoma, and progressive neuroendocrine tumors of pancreatic origin. Its use may be hindered due to adverse events, including rash. The reported incidence and risk of rash to everolimus varies widely and has not been closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology from 1998 to July 2011 using the keyword “everolimus” to identify relevant clinical trials. Eligible studies included prospective phase II and phase III clinical trials of cancer patients on 10 mg of everolimus daily with available data on incidence of rash. The summary incidence and relative risk (RR) of rash were calculated using either the random-effects or fixed-effects model, depending on the heterogeneity of the constituent studies. Results: A total of 2,242 patients with various malignancies from 13 clinical trials were included in the analysis. The summary incidences of all-grade and high-grade rash in patients on everolimus were28.6% (95% CI: 20.8 – 38.0) and 1.0% (95% CI: 0.6 – 1.7), respectively. Everolimus was associated with a statistically significant increased risk of all-grade rash (RR=3.853, 95% CI: 2.470 – 6.013, p=0.000), but the RR for high-grade rash (RR= 2.997, 95% CI: 0.633 – 14.185) was not statistically significant, with a p value of 0.166. Conclusions: Everolimus is associated with a significant risk of developing rash. Management of rash to everolimus is critical to prevent dose modifications and decreased quality of life, both of which can negatively affect clinical outcomes.