Women with advanced hormone receptor positive, HER2 negative breast cancer have had few options for treatment if they have become resistant to aromatase inhibitors, until now. Research presented at the 2016 San Antonio Breast Cancer Symposium found that a combination of everolimus and fulvestrant doubled progression-free survival in these patients compared to fulvestrant alone.
The study enrolled 130 post-menopausal women with HR+, HER2- metastatic breast cancer. All received fulvestrant; 64 also took oral everolimus and 66 took a placebo. Treatment continued until progression. Patient groups were balanced for measurable disease, prior chemotherapy and other stratification factors. After 98 PFS events, median progression-free survival among those taking everolimus was more than twice that of those taking the placebo, 10.4 months versus 5.1 months. The combination reduced the risk of disease progression or death by 39% compared to fulvestrant alone.
The greater effectiveness came with increased adverse effects, however. Grade 3 or 4 AEs occurred in 56% of patients taking everolimus compared to 26% of those in the placebo arm. Among patients receiving everolimus, 16% developed hyperglycemia, 11% had stomatitis, 11% had hypertriglyceridemia, 9% lymphophenia and 8% pneumonitis. No patients on fulvestrant alone developed these AEs. None of the 3 grade 5 events (2 among everolimus patients, 1 among placebo patients) were attributed to therapy. Discontinuation occurred in 39% of everolimus patients and 21% of those in the placebo arm.
The researchers concluded that “the addition of everolimus to fulvestrant significantly improved PFS in post-menopausal women with AI-resistant MBC.”