Everolimus-related adverse events in neuroendocrine tumors and comparative considerations with breast and renal cancer: a critical overview

Introduction: Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is approved as an anti-tumor therapy, as single agent or in combination, for advanced neuroendocrine tumors (NETs), breast and renal carcinomas. Areas covered: In this review we analyzed some general features of everolimus toxicity profile and evidence data about its adverse events (AEs) coming from the most relevant phase III clinical trials. Furthermore we critically discuss this by comparing the different clinical areas of neuroendocrine, breast and kidney malignancies and addressing the clinical management of the everolimus toxicity. Most of the AEs related to everolimus are mild to moderate and manageable with dose reduction or temporary interruptions of therapy. However, a few severe AEs can lead to definitive discontinuation of therapy. Therefore clinicians employing this therapy regardless of tumor type should provide patients with prevention and management strategies in order to increase treatment adherence and improve quality of life (QoL). Risk factors like co administration of other therapies that could interfere with everolimus and increase its toxicity should also be taken into account. Expert opinion: Class adverse effects related to everolimus are similar among clinical trials conducted in solid tumors. Active treatment and monitoring can prevent severe toxicity and unnecessary drug discontinuation that can lead in time to disease progression. Designing future trials and employing toxicity predictive biomarkers are strategies useful for selecting patients that can benefit from mTOR inhibitors.