Women with locally advanced or metastatic hormone receptor-positive breast cancer may strongly benefit from treatment with the estrogen receptor degrader Faslodex (fulvestrant), according to the results of a Phase 3 study.
The findings, recently presented at the European Society for Medical oncology (ESMO) Congress, held Oct. 7–11 in Denmark, reveal that Faslodex improves progression-free survival compared to Arimidex (anastrozole), particularly in patients with less aggressive disease.
The growth of certain types of breast cancer, called hormone receptor-positive cancers, is promoted by the female hormones estrogen and progesterone. In addition to chemotherapy, drugs that inhibit the effects of these hormones are commonly used to treat these cancers.
Unlike aromatase inhibitors such as Arimidex, which decrease the estrogen levels by preventing its production, Faslodex works by binding to estrogen receptors in breast cancer cells, which decreases estrogen binding.
The randomized, double-blind, and multicenter Phase 3 FALCON trial (NCT01602380) was designed to assess the efficacy and tolerability of Faslodex compared to Arimidex in postmenopausal women with ER-positive, HER-negative locally advanced or metastatic breast cancer. The patients had not received any prior hormone therapy.
The study enrolled 462 participants, who were randomized to receive either 500 mg intramuscular Faslodex on days 0, 14, and 28, and then every 28 days, or 1 mg Arimidex daily. Patients were allowed one line of chemotherapy.
After a median follow-up of 25 months, the Faslodex group had a significant, 21 percent improvement in progression-free survival compared to the Arimidex group. Specifically, those taking Faslodex had a median of 16.6 months until disease progression, and those receiving Arimidex had 13.8 months.
But the researchers noted that the effect was even more pronounced in a subgroup analysis. Patients whose disease had not spread to the lungs or liver at baseline had greater progression-free survival benefits when taking Faslodex, compared to those in the Arimidex group (22.3 months vs. 13.8 months).
“For patients with non-visceral disease whose life isn’t immediately threatened by breast cancer — a group for whom physicians would typically choose endocrine therapy as a first approach — it looks like fulvestrant could be a new standard of care compared to anastrozole,” the study’s lead investigator, Dr. Matthew Ellis with the Lester and Sue Smith Breast Center, Baylor College of Medicine in Houston, Texas, said in a press release.
Health-related quality of life was similar in both groups, with the most common adverse events being joint pain and hot flushes.
“It’s tolerated as well as anastrozole, and better than other drugs that could potentially be used in this setting such as chemotherapy or CDK4 inhibitors,” Ellis said. “In patients for whom you are looking for a low toxicity approach, such as older patients or those with low volume disease, it looks like a good option.”
The study also revealed a significantly higher duration of response to treatment in the Faslodex group, which Ellis suggests may account for the increases in progression-free survival seen in these patients.
Dr. Nicholas Turner, team leader at the Institute of Cancer Research and Medical Oncologist at the Royal Marsden, London, believes that these results may lead to important advances in the treatment of breast cancer, but notes that the study has some limitations.
“[T]wo factors complicate moving this new finding into routine clinical practice: firstly, the study only included patients with no prior hormone treatment, yet many patients presenting with advanced breast cancer have previously been treated for the primary breast cancer,” Turner said.
“Secondly, since the design of the study, the standard of care for these women has moved on, with the CDK4/6 inhibitor palbociclib now licensed in US, in combination with an aromatase inhibitor, for the same group of patients,” he added. “Further studies will help define the most optimal sequence of therapy for women with advanced breast cancer.”
Faslodex was approved by the FDA in April 2002 to treat postmenopausal breast cancer patients whose disease has progressed following anti-estrogen therapy. In March of this year, the FDA also approved Faslodex, in combination with Ibrance (palbociclib), for women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer whose disease had progressed following hormone therapy.