Trial Suggests New Treatment Option for Some Women with Metastatic Breast CancerResults from a phase III clinical trial suggest that, for some women with metastatic breast cancer, combining two drugs that work in different ways to disrupt estrogen's ability to fuel cancer growth may delay disease progression and death. The results were published August 2 in the New England Journal of Medicine.
Several breast cancer specialists cautioned, however, that the trial results are not enough to change clinical practice and need to be confirmed.
In the trial, women with metastatic breast cancer treated with the aromatase inhibitor anastrozole (Arimidex) and the antiestrogen fulvestrant (Faslodex) had better progression-free and overall survival than women who were treated with anastrozole alone. Both drugs are already approved to treat metastatic breast cancer.
About 700 women took part in the NCI-funded trial, which was led by SWOG, formerly the Southwest Oncology Group. All of the women in the trial were postmenopausal, had hormone receptor-positive metastatic breast cancer, and had not been previously treated for metastatic cancer. Women in the combination group were given the standard dose of fulvestrant (500 mg) the first time they received it, followed by a lower dose (250 mg) for the remaining treatments. About 40 percent of the women in the anastrozole-only arm began to receive low-dose fulvestrant after their disease began to progress.
Median progression-free survival—the trial's primary endpoint—was 15.0 months in women who received both drugs and 13.5 months in women who received only anastrozole. Overall survival was 47.7 months in the combination therapy arm and 41.3 months in the anastrozole-only arm.
In general, toxic effects were relatively mild and did not differ greatly between the two groups. Nevertheless, 42 patients who received anastrozole alone, and 51 who received both drugs, experienced severe toxic effects, including musculoskeletal pain, flu-like symptoms, and difficulty breathing.
But the results are convincing, said lead investigator Dr. Rita Mehta of the University of California, Irvine, in an interview. "Fulvestrant and anastrozole should be standard for women who would qualify for the study," she said.
But Dr. Jung-Min Lee, of NCI's Medical Oncology Branch, stressed that overall survival was a secondary endpoint of the study and said that several questions need to be answered before the combination therapy is used in clinical practice. "We first have to define the population who might benefit most from the combination therapy," Dr. Lee said. "And we need more data to confirm the overall survival benefit."
The results also conflict with those from a similar international trial, called FACT, which found no difference in overall survival between women who received anastrozole and fulvestrant and women who received anastrozole alone. The trials had several major differences that likely explain the discrepant findings, Dr. Mehta said.
The FACT trial was smaller, she explained, included more women who had received prior tamoxifen (70 percent versus 40 percent), enrolled patients who had completed chemotherapy for earlier-stage disease within the previous 12 months, and was restricted to patients who had suffered a relapse. These differences in the study populations likely "enriched [the trial] for patients with relatively endocrine-resistant disease," she said.
This research was supported by grants from the National Institutes of Health