Phase 3 clinical trial evaluating the safety and efficacy of adding everolimus to exemestane therapy in patients with hormone receptor-positive advanced breast cancer

This phase 3 clinical trial tested whether everolimus (a non-hormonal treatment) added to hormone therapy with exemestane improved survival in patients with advanced breast cancer (BCa). 

Some BCa are fueled by female sex hormones (estrogen or progesterone) that help them grow. These types of cancer are called hormone receptor-positive (HR+) and they respond to hormone therapy. Exemestane (Aromasin) is a type of hormonal therapy which decreases the amount of estrogen the body produces, therefore slowing or stopping the growth of BCa. However, hormonal therapies for BC do not always prevent cancer relapses (return of the cancer). In all cells, including cancer cells, the mTOR (which stands for mammalian target of rapamycin) pathway controls cell survival and division. Cancer relapses are associated with abnormal signals from the mTOR pathway. These abnormal signals allow cancer cells to spread quickly. Drugs that block the mTOR pathway, such as everolimus (Afinitor), are developed to stop cancer relapse. 

This study included 724 women with HR+ advanced BCa. Patients were randomly assigned to one of two treatment groups: group EP (239 patients) received exemestane plus a placebo (a substance with no medical effect used as control when testing new drugs) and group EE (485 patients) received exemestane plus everolimus. The main parameters evaluated were progression-free survival or PFS (defined as the percentage of patients who have survived for a certain period of time, without progression of their cancer) and side effects. Treatment with everolimus plus exemestane for BCa patients more than doubled PFS compared to patients treated with everolimus and placebo (10.6 months versus 4.6 months). However, there were significantly more side effects reported from patients in the EE group compared to patients in the EP group (11% versus 1%). The most common side effects reported were sore mouth, difficulty breathing, high blood sugar levels and tiredness. 

In summary, everolimus combined with exemestane therapy significantly improved PFS in patients with HR+ advanced BCa.

This study had a short follow up period. Future follow up data on these patients is expected to confirm the results of this clinical trial.

This study was funded by Novartis, the manufacturer of Afinitor.