Screening and management of metabolic complications of mTOR inhibitors in real-life settings

Abstract

IntroductionInhibitors of mTOR (mTORi) are frequently used as anticancer treatment. They were responsible for metabolic side-effects in phase 3 studies, which provided only an incomplete picture of these metabolic complications. The aim of our study was therefore to evaluate, in a real-life setting, outcomes for patients with dyslipidemia or diabetes under mTORi, and the incidence and management of metabolic abnormalities occurring under mTORi in the absence of known metabolic history. MethodsThis single-center retrospective study included all 177 patients receiving everolimus in the Cancer Center of Dijon, France, between May 2015 and November 2018. ResultsDiabetes was diagnosed in 15 patients (9%), with an estimated mean time to onset of 160±173 days. Antidiabetic treatment was introduced in 41% of these patients. After mTORi discontinuation, diabetes persisted in 60% of patients in whom it had been diagnosed. Dyslipidemia was diagnosed in 22 patients (14%): 55% with hypercholesterolemia and 45% with hypertriglyceridemia. 18% were placed on lipid-lowering therapy. While all patients were screened for hyperglycemia and monitored for known diabetes, only 42% of patients without dyslipidemia were screened for lipids, and only 8% of patients with known dyslipidemia were monitored for lipids. ConclusionOur study is one of the few to look at metabolic complications secondary to mTORi in a real-life situation. The incidence of diabetes was high, but the use of antidiabetic treatment was variable. Normalization of glucose homeostasis after mTORi discontinuation is possible, particularly in patients who have not been placed on antidiabetic therapy. Screening for dyslipidemia was clearly inadequate in our study, making the data on this point more difficult to interpret. It appears that adherence to guidelines needs to be improved to optimize the management of patients treated with mTORi.