Median progression-free survival – the primary outcome measure – was 13.5 months among the 345 women getting 1 mg of oral anastrozole per day, vs 15.0 months among the 350 who concurrently received 500 mg of fulvestrant followed by 250 mg at 14 days, 28 days and then at one month intervals (p=0.007).
Overall survival, a secondary outcome, rose to 47.7 months with combination therapy from 41.3 months in the anastrozole group (p=0.005), where patients were encouraged to switch to fulvestrant if their cancer progressed. The median follow-up time was 35 months.
Chief author Dr. Rita Mehta of the University of California Irvine Medical Center told Reuters Health the enrollment rules for the study were to designed “to make sure that we got an endocrine-sensitive population.”
“Many of these patients were just diagnosed with metastatic disease at presentation, so about 40% had never been treated with anything, not even a local treatment,” she said in a phone interview.
One twist: for most of the study, which enrolled patients from 2004-2009, the recommended dose for fulvestrant was half of what it is now. The researchers bumped it up to 500 mg in February 2011.
The researchers said there was no significant difference in the rate of grade 3, 4 or 5 toxic side effects.
The most common side effects were musculoskeletal pain, found in 2.8%, influenza-like symptoms, seen in 2.4%, and gastrointestinal problems and hematologic effects, both seen in 1.5%.
“Although grade 3 to 5 toxic effects occurred more frequently in the combination group than in the anastrozole-alone group, the between-group difference was not significant,” the researchers reported.
Both fulvestrant, sold under the brand name Faslodex, and anastrozole, sold as Arimidex, are made by AstraZeneca, which helped finance the study.
Based on the new findings, the combination “should be the standard,” said Dr. Mehta. “It’s been my standard since we got the results of the study.”