By Gene Emery
(Reuters Health) - 27/3/2019
More than six years after a study showed that women with hormone-receptor-positive metastatic breast cancer benefit from a combination of anastrozole and fulvestrant, extended results show the trend has become even more pronounced, but mostly for women not previously exposed to tamoxifen.
In the test, the final results of which were reported online March 27 in The New England Journal of Medicine, overall survival was 49.8 months with combination therapy and 42.0 months in the anastrozole group (P=0.03), where patients were encouraged to switch to fulvestrant if their cancer progressed, which about 45% of them did. The median follow-up time was 7 years.
The big difference was seen in women who had not previously received tamoxifen. Median survival for those 414 patients was 52.2 months with combination therapy versus 40.3 months with anastrozole but not fulvestrant (hazard ratio of 0.73 with a 95% confidence interval of 0.58 to 0.92).
Among the 280 women who had previous exposure to adjuvant tamoxifen, median overall survival was 48.2 months with fulvestrant and anastrozole versus 43.5 months without fulvestrant (hazard ratio of 0.97 with a 95% confidence interval of 0.74 to 1.27).
Few patients in either group discontinued their treatment due to side effects.
"This is the probably the only study that has reached statistical significance in proving overall survival in hormone-receptor-positive patients," chief author Dr. Rita S Mehta of the Chao Family Comprehensive Cancer Center in Orange, California, told Reuters Health in a telephone interview.
An estimated 6% of women with breast cancer -- about 16,000 just in the United States -- present with stage IV disease at diagnosis. The worldwide rate is roughly 20% to 30%, said Dr. Mehta.
"It's important for patients to know that they can go on a treatment that doesn't cause hair loss, that doesn't cause a reduction in white cells or platelets, that doesn't cause increased infection," she said. "This agent doesn't cause any of these immunosuppressive effects. It means many of these patients can have an excellent quality of life."
Both fulvestrant, sold under the brand name Faslodex, and anastrozole, sold as Arimidex, are made by AstraZeneca, which helped finance the study.
Median progression-free survival rates showed a similar trend to overall survival.
It was 15.0 months with combination therapy and 13.5 months in the anastrozole-alone group (P=0.007).
Women who had not previously received tamoxifen therapy were the big beneficiaries if they received the combination treatment. Median progression-free survival was 16.7 months with combination therapy and 12.7 months with anastrozole alone.
Among the 40% of the women with previous exposure to adjuvant tamoxifen, median progression-free survival was 13.9 months with fulvestrant and 13.6 months without.
But taking tamoxifen in the past doesn't necessarily mean the drug combination won't be beneficial, Dr. Mehta said.
"If you have an adequate tamoxifen-free interval of more than a year, you can still use fulvestrant and anastrozole and get a good outcome," she said. "If patients have been on tamoxifen recently, the benefit of fulvestrant may not accrue." And the many women with early breast cancer who fail to comply with tamoxifen treatment might benefit from this therapy if their cancer advances, said Dr. Mehta. "Twenty to 40 percent stop taking their medicine," she said. "So at the time of metastases, a good percentage turn out to be tamoxifen non-exposed. And if they've been exposed to tamoxifen in the distant past, they can still benefit from fulvestrant. By that time, I tell my fellows, the tumor doesn't remember it's been treated with tamoxifen."
The most common side effects were musculoskeletal pain, which appeared in 2.8% of patients, influenza-like symptoms, seen in 2.4%, and gastrointestinal problems and hematologic effects, both seen in 1.5%.
SOURCE: https://bit.ly/2FxAWfN N Engl J Med 2019.