Everolimus

Everolimus is an oral targeted anticancer and immunosuppressant agent. It is a rapalog, an analog of sirolimus, that inhibits mammalian target of rapamycin complex 1 (mTORC1) by forming a complex with FKBP12. Inhibition of mTORC1 blocks signaling pathways that promote cell growth, proliferation, angiogenesis, and survival in various tumor and immune cells.

In medicine, everolimus is approved for multiple indications. In oncology, it is used for advanced renal cell carcinoma after failure of VEGF-targeted therapy, and for certain neuroendocrine tumors including pancreatic neuroendocrine tumors; as well as for breast cancer: hormone receptor-positive, HER2-negative advanced disease following progression on aromatase inhibitors. In tuberous sclerosis complex–associated diseases, it is approved to treat renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA). It is also used off-label in other conditions where mTOR pathway is implicated.

Pharmacokinetics and administration: Everolimus is taken orally, usually once daily, with dose adjusted by indication and patient tolerance. It is metabolized primarily by CYP3A4 and is subject to drug interactions with inhibitors and inducers of this enzyme. It has a relatively long half-life and variable bioavailability. The drug is associated with adverse effects including stomatitis/mucositis, infections, edema, cytopenias, hyperlipidemia, hyperglycemia, liver function test abnormalities, pneumonitis, and wound-healing impairment. Because of immunosuppressive effects, care is taken in patients with active infections or poor wound healing, and use during pregnancy is contraindicated unless potential benefit justifies risk.

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