The FDA has approved everolimus tablets (Afinitor) for use in combination with exemestane to treat postmenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer after failure of treatment with letrozole or anastrozole.
The approval was based on a randomized, double-blind, multicenter trial conducted in 724 postmenopausal women with estrogen receptor–positive, HER2-negative, advanced breast cancer with recurrence or progression following prior therapy with letrozole or anastrozole. Patients were randomly allocated to everolimus 10 mg/d plus exemestane 25 mg/d (n = 485) or to placebo plus exemestane 25 mg/d (n = 239). Patients were not permitted to cross over to everolimus at the time of disease progression.
The median progression-free survival at the time of final analysis was 7.8 and 3.2 months in the everolimus and placebo arms, respectively (HR 0.45 [95% CI: 0.38, 0.54], P < .0001). The objective response rates were 12.6% and 1.7% in the everolimus and placebo arms, respectively. An interim analysis of overall survival conducted at 46% of expected events was not statistically significant (HR 0.77 [95% CI: 0.57, 1.04]). The final analysis of overall survival is expected to be performed in June 2014.
The most common side effects observed in patients were mouth ulcers, infections, rash, fatigue, diarrhea, and decreased appetite. Patients aged 65 years and older should be monitored closely as these patients experience a higher rate of serious side effects than younger patients receiving the treatment.
Forty percent of patients on the everolimus arm were aged 65 years and older, and 15% were aged 75 years and older. No overall differences in effectiveness were observed between elderly and younger patients. The incidence of deaths due to any cause within 28 days of the last everolimus dose was 6% in patients aged 65 years and older compared to 2% in patients younger than 65 years of age.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022334s016lbl.pdf ■