title: Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer.
abstract: 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.
  
  
  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.
authors.affiliation: Multidisciplinary Oncology Institute, Clinique de Genolier, Genolier, Switzerland. Electronic address: maapro@genolier.net.
authors.forename: M
authors.initials: M
authors.lastname: Aapro
authors.affiliation: French National Institute of Health and Medical Research (INSERM), Université Paris Sud, Orsay; Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Andre
authors.affiliation: Department of Medicine/Medical Oncology, Duke University Medical Center, Durham, USA.
authors.forename: K
authors.initials: K
authors.lastname: Blackwell
authors.affiliation: Melanoma Program, Centro Integral Oncológico Clara Campal and Clinical Research, START Madrid, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jahanzeb
authors.affiliation: Department of Medical Oncology, Euromedica General Clinic, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Papazisis
authors.affiliation: Department of Medical Oncology, IRCCS, San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.affiliation: Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Pritchard
authors.affiliation: Department of Medical Oncology, Hôpital Saint-Andre, Bordeaux University Hospital, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Ravaud
mesh_terms: D000284:Administration, Oral; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000068338:Everolimus; D020123:Sirolimus
keywords: everolimus; infections; metabolic abnormality; pneumonitis; rash; stomatitis