Long-term efficacy and safety of exemestane in the treatment of breast cancer
GA Walker,1 M Xenophontos,2 LC Chen,3 KL Cheung2
1Clinical Oncology, East Midlands Deanery, 2Breast Surgery, School of Graduate Entry Medicine and Health; 3Medicine Use, School of Pharmacy, University of Nottingham, Nottingham, UK
Abstract: Exemestane, a steroidal aromatase inhibitor, is licensed for postmenopausal patients with estrogen receptor (ER)-positive breast cancer as second-line therapy in metastatic disease following antiestrogen failure and as part of sequential adjuvant therapy following initial tamoxifen. This study is a systematic literature review, evaluating exemestane in different clinical settings. The Ovid Medline (1948–2012), Embase (1980–2012), and Web of Science (1899–2012) databases were searched. Forty-two relevant articles covering randomized controlled trials were reviewed for efficacy and safety, and three for adherence. With regard to efficacy in metastatic disease, exemestane is superior to megestrol acetate after progression on tamoxifen. There is evidence for noninferiority to fulvestrant (following a prior aromatase inhibitor) and to nonsteroidal aromatase inhibitors in the first-line setting. Combined use with everolimus is shown to be more efficacious than exemestane alone following previous aromatase inhibitor use. In the adjuvant setting, a switch to exemestane after 2–3 years of tamoxifen is superior to 5 years of tamoxifen. Exemestane is noninferior to 5 years of tamoxifen as upfront therapy, and may have a role as an extended adjuvant therapy. Used as neoadjuvant therapy, increased breast conservation is achievable. As chemoprevention, exemestane significantly reduces the incidence of breast cancer in “at-risk” postmenopausal women. Exemestane is associated with myalgias and arthralgias, as well as reduced bone mineral density and increased risk of fracture, which do not appear to persist at follow-up, with subsequent return to pretreatment values. Compared with tamoxifen, there is a reduced incidence of endometrial changes, thromboembolic events, and hot flashes. Limited evidence shows nonadherence in 23%–32% of patients. Evidence is growing in support of exemestane in all clinical settings. It is generally more efficacious and has a better safety profile than tamoxifen. How it compares with the nonsteroidal aromatase inhibitors remains to be established. Further studies are required on adherence to ensure that maximum benefit is obtained.
Keywords: breast cancer, exemestane, review, adherence, metastatic, adjuvant
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