Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis

Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, its specific impact on hyperglycemia has not been well understood. We performed a meta-analysis of randomized controlled trials to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Material and methods: PubMed and American Society of Clinical Oncology conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without other agents. Heterogeneity tests were performed to examine between-study differences in hyperglycemia, and the incidence and relative risk of all- and high-grade hyperglycemia attributable to everolimus were determined using both random- or fixed-effects models. Results: A total of seven phase III and two phase II RCTs with various tumors, encompassing a total of 3879 cancer patients, were included in our analysis. Everolimus significantly increased the risk of all-grade (RR =2.60, 95% CI 2.03–3.31, p < 0.001) and high-grade (RR =3.0, 95% CI 1.72–5.23; p < 0.001) hyperglycemia. The incidences of all- and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI 3.4–13.2%) and 2.5% (95% CI 1.2–4.9%), respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (p < 0.001), with the highest incidence seen in renal cell carcinoma (RCC) (27.2%, 95% CI 22.2–32.8%) and the lowest in breast cancer (3.3%, 95% CI 1.3–8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusion: The specific risk of hyperglycemia attributable to everolimus may vary significantly with tumor types. Close monitoring should be given to patients at high risk, such as RCC.