Results of a SWOG clinical trial published August 2 in the New England Journal of Medicine show the combination of anastrozole and fulvestrant extended the median survival time of women with hormone receptor-positive metastatic breast cancer by more than six months compared to women treated with a standard therapy of anastrozole alone (47.7 months vs. 41.3 months).

The combination therapy also lengthened the median time to disease progression for these patients (15 months vs. 13.5 months). Progression-free survival time was the primary endpoint measured in the trial; overall survival time was a secondary endpoint.

"The combination offers a new standard for first-line treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer," says lead investigator on the study Rita Mehta, M.D., of the University of California, Irvine Medical Center. "It has been many years since these patients have seen a new treatment that can significantly extend their overall survival time."

Anastrozole and fulvestrant, the anti-estrogen drugs included in the SWOG S0226 trial, are both already used in treating breast cancer, though not in combination. Anastrozole suppresses the body's production of tumor-promoting estrogen, while fulvestrant not only blocks the receptors that estrogen uses to drive tumor cells to grow and reproduce, but also accelerates the degradation of these receptors. Mehta and her colleagues hypothesized that these two different modes of action together could make the combination more effective than either alone against hormone receptor-positive breast cancer, the subtype seen in more than one half of all cases of breast cancer.]

The study included 707 postmenopausal women who had metastatic breast cancer that was hormone-receptor-positive. About half the women were randomly assigned to receive the standard regimen: treat first with anastrozole, and after the disease progresses, switch to fulvestrant. The other half were randomly assigned to receive anastrozole and fulvestrant in combination.

Women who received the standard regimen survived a median of 41.3 months. Women who received the two drugs in combination survived a median of 47.7 months.

Among women who received the standard regimen, it took a median of 13.5 months for the disease to progress. Among those who received the drugs in combination, it took 15 months before the disease progressed.

The combination treatment produced even greater benefits among women who had not previously taken tamoxifen.

Side effects generally were similar in both treatment groups, although only the combination group experienced the most severe side effects (one stroke and two pulmonary embolisms).

The paper also reports that 41 percent of patients on the anastrozole-only arm switched to fulvestrant treatment after their disease progressed on anastrozole, suggesting that combined use of the two agents rather than the sequential use underlies the impressive survival benefit seen in the study.

Earlier results of the trial, which enrolled 707 postmenopausal breast cancer patients at 73 U.S. institutions, were presented at a professional meeting in December 2012. The New England Journal of Medicine article reports additional data.

The researchers note that they saw improvement in survival in spite of the fact that the dose of fulvestrant used in the trial – 250 mg monthly – was only half of what the accepted standard is today, and in spite of the fact that the control arm performed better than projected in the design of the study. They recommend that future clinical trials compare the combination of high-dose fulvestrant and an aromatase inhibitor such as anastrozole against each of the drugs alone.

Funding for SWOG S0226 came primarily from the National Cancer Institute, one of the National Institutes of Health. Additional support, and the anastrozole and fulvestrant for the trial, were provided by AstraZeneca Pharmaceuticals LP, of Wilmington, Del.

Other authors on the abstract include WE Barlow and DL Lew of the SWOG Statistical Center, KS Albain of Loyola University, TA Vandenberg of London Regional Cancer Centre/NCIC-CTG, SR Dakhil of Wichita CCOP, NR Tirumali of Northwest CCOP, DF Hayes of University of Michigan, JR Gralow of Seattle Cancer Care Alliance, RB Livingston of University of Arizona, and GN Hortobagyi of MD Anderson.