MedWire News: Phase III trial results show that a combination of the aromatase inhibitor anastrozole and fulvestrant, an analog of estradiol that downgrades the estrogen receptor, is superior to anastrozole alone in prolonging progression-free survival (PFS) in patients with metastatic breast cancer.
Not only was PFS longer in women treated with the combination therapy, but their overall survival was longer too, writes the research team in the New England Journal of Medicine.
Despite both regimens being associated with mild-to-moderate toxic effects and more grade 3-5 effects occurring in the combination group than the anastrozole-only group, "the between-group difference was not significant," say Rita Mehta (University of California Irvine Medical Center, Orange, USA) and co-researchers.
The team randomly assigned 694 postmenopausal women with hormone receptor-positive metastatic breast cancer in a 1:1 ratio to receive either anastrozole 1 mg/day (group 1), or the same anastrozole regimen plus an initial loading dose of fulvestrant 500 mg on day 1, followed by fulvestrant 250 mg on days 14 and 28 and then every 28 days (group 2).
After the 4-year follow-up period, 565 women either experienced progression or died; 297 from group 1 and 268 from group 2. The median PFS was 13.5 months in group 1 compared with 15.0 months in group 2, and as time passed, the superiority of combination therapy emerged.
For example, PFS at 1 year was 56% in group 1 and 57% in group 2, at 2 years these rates were 28% and 35%, and by 3 years, the respective rates were 16% and 25%.
A similar pattern emerged for overall survival rates, note the authors. After a respective median overall survival of 41.3 months and 47.7 months there were 176 deaths in group 1 and 154 in group 2.
Over time, however, the magnitude of difference between groups increased: the rate of overall survival at 1 year was 89% in group 1 and 91% in group 2, at 2 years was 75% and 79%, and by 3 years, was 57% and 62%.
In all, patients who received combination therapy were 20% less likely than those who received anastrozole alone to experience progression and 19% less likely to die during the study follow-up, report Mehta et al.
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