Combination of Anastrozole and Fulvestrant therapy in hormone receptor positive metastatic breast cancer

This study compared the effect of two regimens for hormone-positive, metastatic breast cancer on disease progression and survival: a combination of two drugs, namely anastrozole (Arimidex) and fulvestrant (Faslodex), versus anastrozole alone. 

Breast cancers often require estrogen (the female sex hormone) to grow. Estrogen’s effect is mediated by a structure called ‘receptor’ present on the cell surface. These estrogen-dependent breast cancers are called ‘hormone-receptor positive (HR+) breast cancers’.

Aromatase inhibitors (AIs) are a class of drugs used in the treatment of HR+ breast cancers in postmenopausal women. They act by lowering the levels of estrogen in the blood. Anastrozole is a type of AI.

Fulvestrant  is an estrogen-like protein that reduces the availability of estrogen receptors, and decreases tumor resistance to hormone therapy.

694 Postmenopausal women with HR+ metastatic breast cancer (a cancer that has spread beyond the breast to distant organs) were randomly assigned into two groups. Group 1 received a single drug, 1 mg of anastrozole orally every day . Group 2 received a multidrug therapy consisting of anastrozole in combination with fulvestrant, given by intramuscular injection at doses of 500 mg on day 1, 250 mg on days 14 and 28, and monthly afterwards. Patients in group 1 whose disease progressed were encouraged to switch to fulvestrant therapy alone and remain in the trial, thereby treated ‘sequentially’. Participants did not receive any prior treatment (hormonal or chemotherapy) for metastatic breast cancer.

Results showed that combination therapy was generally more effective than a single drug regimen. The time until progression of the disease in group 1 was 12.1-15.1 months, compared to 13.2-18.4 months in group 2. Overall survival was also longer with combination therapy; 37.2-45.0 months in group 1 versus  43.4-55.7 months in group 2.

Both drug regimens were associated with mild-to-moderate toxic effects, and although sever toxic effects occurred more frequently in group 2, the difference was not significant.

The combination of anastrozole and fulvestrant as first line treatment for HR+ metastatic breast cancer was superior to treatment with anastrozole alone, and to sequential treatment consisting of anastrozole followed by fulvestrant.

Prior studies have failed to show the superiority of multidrug therapy over single agents, particularly with respect to overall survival. However, these studies included patients with different characteristics compared to the present trial. 

Nowadays the FDA has approved a higher monthly dose of fulvestrant (500 mg) in the treatment of HR+ metastatic breast cancer, since it showed superior activity to the lower dose (250mg), tested in the present study. Talk to your doctor about available regimens for HR+ metastatic breast cancer.