title: Everolimus in combination with exemestane: a review of its use in the treatment of patients with postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer.
abstract: Oral everolimus (Afinitor(®)) in combination with exemestane is indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer in postmenopausal women after failure of treatment with letrozole or anastrozole (in the USA) or after recurrence of progression following a nonsteroidal aromatase inhibitor (AI) in women without symptomatic visceral disease (in the EU). Everolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), inhibits the downstream signalling events of the mTOR pathway. This review summarizes the pharmacology of everolimus and reviews its efficacy and tolerability when administered in combination with exemestane in postmenopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer refractory to nonsteroidal AIs. In the well-designed BOLERO-2 study, the addition of everolimus to exemestane was shown to significantly prolong progression-free survival in this patient population. However, treatment-emergent adverse events and treatment discontinuations occurred more frequently with combination therapy than with exemestane alone, suggesting a need for careful benefit/risk assessment prior to initiating therapy. Mature survival data from this study are awaited and additional studies would help to further demonstrate the benefit of combination therapy. Nevertheless, current evidence suggests that everolimus plus exemestane combination therapy may be a useful treatment option in patients with postmenopausal hormone receptor-positive, HER2-negative, advanced breast cancer refractory to nonsteroidal AIs.
authors.affiliation: Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754 Auckland, New Zealand. demail@springer.com
authors.forename: Sohita
authors.initials: S
authors.lastname: Dhillon
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D055502:Secondary Prevention; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D000068338:Everolimus; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; C508053:ERBB2 protein, human; C056516:exemestane