First-line treatment with Arimidex (anastrozole) plus Faslodex (fulvestrant) prolongs the lives of post-menopausal women with hormone receptor (HR)-positive advanced breast cancer, particularly those who have never taken tamoxifen, results of a clinical trial show.
The study, “Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer,” was published in the New England Journal of Medicine.
Faslodex, developed by AstraZeneca, is approved for HR-positive advanced breast cancer in women who have been through menopause, including those who have not received prior hormone therapy, also known as endocrine therapy (e.g. the anti-estrogen medication tamoxifen), and those whose cancer got worse after taking a hormonal treatment.
Is is also indicated as an add-on treatment for women with HR-positive breast tumors whose cancer has spread to other parts of the body and has worsened following hormone therapy.
Faslodex is also an anti-estrogen drug. It works by selectively blocking estrogen receptors, halting that hormone’s effect on tumor cells. As a consequence, it slows or stops the growth of HR-positive breast cancers, which depend on estrogen to proliferate.
Arimidex, also by AstraZeneca, is also a hormonal therapy, but prevents the effects of estrogen through a different mechanism. It is an aromatase inhibitor, blocking the production of estrogen by inhibiting aromatase, an enzyme necessary for this process.
The medicine is used primarily in post-menopausal women because before menopause the ovaries produce too much aromatase for the inhibitor to block them effectively.
But despite treatment with Arimidex, postmenopausal women with advanced breast cancer have a poor prognosis. In some cases, tumors become resistant to treatment because they become reactive to very low levels of estrogen.
Researchers from the Southwest Oncology Group (SWOG) reasoned that combining Arimidex with a blocker of estrogen signaling such as Faslodex could favor the response of women with such tumors.
To test this, they conducted a Phase 3 trial (S0266) (NCT00075764), sponsored by SWOG in collaboration with the National Cancer Institute (NCI).
The trial’s goal was to compare the safety and efficacy of Faslodex plus Arimidex versus Arimidex alone as a first-line treatment for post-menopausal women with HR-positive metastatic breast cancer.
The study enrolled 707 patients, 694 of whom had eligible data for analysis. Participants were treated in 28-day cycles and were randomized to one of two groups. One group received a tablet of Arimidex once a day; the other received Arimidex plus Faslodex, injected into the muscle on days 1, 14, and 28 on the first cycle, followed by a maintenance and lower dose of Fasdolex, given on day 28 of the subsequent cycles.
Earlier results at a median follow-up of three years showed that compared to Arimidex alone, the combination of Faslodex and Arimidex slightly prolonged overall survival and progression-free survival — the time to cancer worsening or death.
In the present report, researchers presented updated, long-term survival data, relative to a median follow-up of seven years in patients without disease progression.
The results showed the combo therapy extended overall survival from 42 months — seen with Arimidex only — to a median 49.8 months. Median progression-free survival was 15.9 months in those taking the combo therapy group and 13.5 months in those receiving Arimidex only.
A more detailed analysis, where patients with and without prior tamoxifen were separated, revealed the combination benefited mostly those patients who never had taken tamoxifen.
Overall survival was longer in women who had not received tamoxifen and took the combination therapy, compared with those given Arimidex alone — 52.2 months versus 40.3 months.
In contrast, for those women who had received tamoxifen, no significant differences in overall survival were found between the two treatment groups — 48.2 months and 43.5 months.
The safety profile was similar between both treatment regimens, with a comparable incidence of long-term toxic effects that were serious, life-threatening, or resulting in death. Serious toxic effects occurred in 15% of the combination group and in 13% in the Arimidex group.
These events included musculoskeletal pain, fatigue, hot flashes, mood alterations, and gastrointestinal symptoms. Few patients withdrew treatment owing to adverse events or side effects — five in the Arimidex group and 12 in the combo therapy group.
Moreover, about 45% of the patients in the Arimidex group crossed over to receive Faslodex only.
The significant survival benefit with the combination therapy surpassed what researchers had projected at the beginning of the trial.
In conclusion, they said, “the combination of the selective estrogen-receptor down-regulator fulvestrant [Faslodex] and the aromatase inhibitor anastrozole [Arimidex], given as first-line endocrine therapy, resulted in superior long-term progression-free survival and overall survival, as compared with anastrozole alone, among post-menopausal women with HR-positive metastatic breast cancer.”
They say this holds true even when the efficacy of combo therapy is compared with sequential treatment; that is, first taking Arimidex and then Faslodex, as in those patients who crossed over.
Moreover, the superiority of the combo was seen despite the use of a maintenance dose of Faslodex (starting at the second month of treatment) that was lower than the now-standard higher dose (i.e., 250 mg rather than 500 mg per month).
The team also stressed that the trial results suggest “the benefits were particularly notable in women who had not received endocrine therapy [e.g. tamoxifen] previously.”