RT Journal Article SR Electronic T1 Risk of Anemia Attributable to Everolimus in Patients with Cancer: A Meta-analysis of Randomized Controlled Trials JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2333 OP 2340 VO 35 IS 4 A1 RAJI SHAMEEM A1 MUHAMMAD SAAD HAMID A1 SHENHONG WU YR 2015 UL http://ar.iiarjournals.org/content/35/4/2333.abstract AB Background: Everolimus, an inhibitor of mammalian target of rapamycin (mTOR) used for the treatment of various solid tumors, is associated with anemia, which can lead to morbidity and treatment interruption or discontinuation. Because the underlying causes of anemia can be multifactorial, we performed a meta-analysis of randomized controlled trials (RCTs) to determine the overall risk of anemia specifically attributable to everolimus in cancer patients. Materials and Methods: We searched the PubMed database and abstracts presented at the American Society of Clinical Oncology annual meetings up to May 2014 for relevant studies. Eligible studies included RCTs in which everolimus alone or in combination with other agents was compared to placebo alone or with other agents in patients with cancer. Summary incidences, relative risks (RR), and 95% confidence intervals (CI) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included trials. The attributable risk was determined by the incidence with everolimus minus that without everolimus in controls. Results: A total of nine RCTs with 3,678 patients (everolimus, n=2,162; controls, n=1,516) were included in our analysis. In comparison with controls, everolimus significantly increased the risk of all-grade (RR=2.18, 95% CI=1.56-3.04, p<0.001) and high-grade anemia (RR=2.63, 95% CI=1.35-5.15, p<0.001). The summary incidences of all-grade (grades 1-4) and high-grade (grades 3-4) anemia in patients treated with everolimus were 32.1% (95% CI=17.5-51.3%) and 6.9% (95% CI=4.1-11.3%) respectively, with 13.3% (95% CI=10.0-17.5%) and 4.7% (95% CI=2.8-7.7%) specifically attributable to everolimus. Risk factors of high-grade anemia attributable to everolimus included tumor type (p=0.012), with the highest seen in renal cell carcinoma (8.0%, 95% CI=5.3-11.9%), and chemotherapy (p<0.001). Conclusion: There is a substantial risk of all-grade and high-grade anemia attributable to everolimus therapy for cancer.