Rash to the mTOR inhibitor everolimus: Systematic review and meta-analysis Journal Article


Authors: Ramirez-Fort, M. K.; Case, E. C.; Rosen, A. C.; Cerci, F. B.; Wu, S. H.; Lacouture, M. E.
Article Title: Rash to the mTOR inhibitor everolimus: Systematic review and meta-analysis
Abstract: Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for treatment of renal cell carcinoma, subependymal giant cell astrocytoma, breast cancer, and progressive neuroendocrine tumors of pancreatic origin. Its use may be hindered because of adverse events, including rash. The reported incidence and risk of a 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 a rash. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology from 1998 to December 2011 using the keyword "everolimus" to identify relevant clinical trials. Eligible studies included prospective phase II and 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 2242 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 were 28.6% [95% confidence interval (CI), 20.8-38.0] and 1.0% (95% CI, 0.6-1.8), 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 a rash. Management of rash to everolimus is critical to prevent dose modifications and decreased quality of life, both of which can negatively affect overall clinical outcomes.
Keywords: in-vitro; management; everolimus; rapamycin; mtor inhibitor; breast-cancer; clinical-trials; phase-ii; renal-cell carcinoma; mammalian target; egfr inhibitors; transplant recipients; skin rash
Journal Title: American Journal of Clinical Oncology
Volume: 37
Issue: 3
ISSN: 0277-3732
Publisher: Lippincott Williams & Wilkins  
Date Published: 2014-06-01
Start Page: 266
End Page: 271
Language: English
ACCESSION: WOS:000336958200009
DOI: 10.1097/COC.0b013e318277d62f
PROVIDER: wos
PUBMED: 23241507
Notes: Review -- Source: Wos
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Mario E Lacouture
    457 Lacouture
  2. Alyx C Rosen
    20 Rosen
  3. Emily C Case
    3 Case