Researchers found that when two agents designed to treat breast cancer—anastrozole (Arimidex, AstraZeneca) and fulvestrant (Faslodex, AstraZeneca)—are given in combination, patients with metastatic breast cancer experienced longer periods of progression-free survival (PFS) and overall survival (OS) compared to patients who received either anastrozole alone or sequential anastrozole and fulvestrant.
The results of the phase III, randomized trial were published online by The New England Journal of Medicine
earlier this month.
The two therapies have already received approval to treat breast cancer. Anastrozole is an aromatase inhibitor that lowers the estrogen level and is typically prescribed as a first-line endocrine treatment in breast cancer patients with HR-positive metastatic disease. Fulvestrant disrupts estrogen receptor and estrogen-independent growth factor signaling, which delays resistance to hormonal therapy.
The study enrolled postmenopausal women with previously untreated metastatic disease who were randomly assigned to receive either 1 mg of anastrozole orally once daily in combination with injections of fulvestrant, which were given in sequential dosing on the first day, every two weeks, and then once every 28 days after the first month, or 1 mg of anastrozole orally once daily with crossover possible to fulvestrant alone. The researchers collected data from 694 patients in the intention-to-treat population.
Patients in the combination group experienced a median PFS of 15.0 months compared to 13.5 months in the anastrozole-alone group (HR=0.80; 95% CI, 0.68-0.94, P
= .007). The combination group also experienced a higher median OS of 47.7 months compared to 41.3 months in the anastrozole-alone group (HR=0.81; 95% CI, 0.65-1.00, P
= .05), even though 143 of the patients in the anastrozole-alone arm (41.4%) crossed over to fulvestrant after progression. In the combination arm, 51 patients had toxic effects of grade 3 or higher (14.7%) compared to 42 patients in the anastrozole-alone arm (12.7%) (P
“The improvement in overall survival that was observed in our study has not been seen in other trials of first-line hormonal therapy for HR-positive metastatic breast cancer,” the authors wrote.
The authors also noted that the benefit was not the result of fulvestrant alone. They referenced a study that compared low-dose fulvestrant to tamoxifen that did not show a between-group difference in PFS or OS, suggesting that in this study, the combination therapy was responsible for the improved survival rather than fulvestrant alone.
The authors suggest that further trials of adjuvant therapy in patients with metastatic breast cancer should compare high-dose fulvestrant and an aromatase inhibitor to either an aromatase inhibitor alone or high-dose fulvestrant alone in patients with estrogen-receptor-positive tumors.
Mehta RS, Barlow WE, Albain KS, et al. Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer [published online ahead of print August 2, 2012]. N Engl J Med. 2012; 367(5): 435-444.