BACKGROUND: Everolimus, an orally administered rapamycin analogue, inhibits the 
mammalian target of rapamycin (mTOR), a highly conserved intracellular 
serine-threonine kinase that is a central node in a network of signaling 
pathways controlling cellular metabolism, growth, survival, proliferation, 
angiogenesis, and immune function. Everolimus has demonstrated substantial 
clinical benefit in randomized, controlled, phase III studies leading to 
approval for the treatment of advanced renal cell carcinoma, advanced 
neuroendocrine tumors of pancreatic origin, renal angiomyolipoma and 
subependymal giant-cell astrocytoma associated with tuberous sclerosis complex, 
as well as advanced hormone-receptor-positive (HR(+)) and human epidermal growth 
factor receptor-2-negative advanced breast cancer.
MATERIALS AND METHODS: We discuss clinically relevant everolimus-related adverse 
events from the phase III studies, including stomatitis, noninfectious 
pneumonitis, rash, selected metabolic abnormalities, and infections, with focus 
on appropriate clinical management of these events and specific considerations 
in patients with breast cancer.
RESULTS: The majority of adverse events experienced during everolimus therapy 
are of mild to moderate severity. The safety profile and protocols for toxicity 
management are well established. The class-effect adverse event profile observed 
with everolimus plus endocrine therapy in breast cancer is (as expected) 
distinct from that of endocrine therapy alone, but is similar to that observed 
with everolimus in other solid tumors. Information gained from the experience in 
other carcinomas on prompt diagnosis and treatments to optimize drug exposure, 
treatment outcomes, and patients' quality of life also applies to the patient 
population with advanced breast cancer.
CONCLUSIONS: As with all orally administered agents, education of both 
physicians and patients in the management of adverse events for patients 
receiving everolimus is critical to achieving optimal exposure and clinical 
benefit. Active monitoring for early identification of everolimus-related 
adverse events combined with aggressive and appropriate intervention should lead 
to a reduction in the severity and duration of the event.