Results from a phase 3 clinical trial presented in early December at the 34th Annual San Antonio Breast Cancer Symposium showed that adding the drug everolimus (Afinitor) to exemestane (Aromasin) significantly prolonged progression-free survival of post-menopausal women with advanced estrogen receptor-positive (ER+) breast cancer. The results generated considerable excitement at the conference; some oncologists speculate that the combination could become a new standard of care for this patient population.

Women with advanced or metastatic ER+ breast cancer who become refractory to hormonal therapy have limited options for secondary treatment. Everolimus is an mTOR inhibitor, a type of drug that interferes with critical growth signals within cancer cells. mTOR inhibitors also have antiangiogenic activity, meaning that they inhibit the ability of tumors to grow a blood supply. Previous smaller studies and preclinical work has demonstrated that activation of the mTOR signaling pathway is associated with resistance to hormonal therapy in ER+ breast cancer, and that drugs that inhibit mTOR signaling, like everolimus, can help overcome this resistance. 

The new study, called BOLERO-2, involved 724 post-menopausal women with advanced ER+, HER-2-negative breast cancer who had been previously treated with and had become resistant to the non-steroidal aromatase inhibitors letrozole and anastrozole. The women were randomly assigned in a 2-to-1 ratio to receive exemestane, a steroidal aromatase inhibitor, plus either everolimus or a placebo. Results showed a median progression-free survival (the amount of time a patient lives without her disease getting worse) of 7.4 months for the everolimus group compared with 3.2 months for the placebo group, a highly significant difference. The clinical benefit rate, which included all patients in whom tumors either shrank or stopped growing, was 50.5% for the everolimus arm versus 25.5% for the placebo arm. However, substantially more patients who received combination therapy discontinued treatment due to side effects (19%) compared with those in the placebo group (4%). 

Everolimus, which is taken as a pill, is currently FDA approved to treat advanced kidney cancer and a type of pancreatic cancer called a neuroendocrine tumor. Oncologists will have the option of using everolimus “off-label” to treat their breast cancer patients. Exemestane, also taken orally, is widely used as adjuvant therapy for ER+ breast cancer.