FASLODEX 500 mg

December 11, 2009 (San Antonio, Texas) — Clinicians using fulvestrant (Faslodex, AstraZeneca) in breast cancer patients who have progressed to metastatic disease on other hormonal therapies might want to consider a 500 mg dose instead of the currently approved 250 mg dose.

New data presented here at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS) show that the higher dose provided a statistically significantly longer time to disease progression than the 250 mg dose (6.5 vs 5.5 months; P = .006).

The results come from the CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial.

Fulvestrant is a somewhat forgotten, or at least overshadowed, hormonal therapy for breast cancer, suggested C. Kent Osborne, MD, director of the SABCS meeting and moderator of the press conference during which the CONFIRM trial data were presented.

"The issues with fulvestrant include the fact that it is a once-a-month intramuscular injection, as opposed to a daily oral hormonal therapy, and that aromatase inhibitors came along first," said Dr. Osborne, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine in Houston, Texas.

In an earlier study, 250 mg of "fulvestrant was as good as [anastrozole]" in estrogen-receptor-positive patients with advanced disease who had progressed on previous hormonal therapy, explained Dr. Osborne.

However, Dr. Osborne said, the drug is limited to metastatic patients who have progressed on tamoxifen and aromatase inhibitors and "allows some control before the patient goes on to chemotherapy."

The new results with 500 mg of fulvestrant do not change its place in the algorithm of hormone-receptor-positive breast cancer treatments, explained Angelo Di Leo, MD, PhD, director of the Department of Oncology at the Hospital of Prato in Italy, and lead author of the CONFIRM study.

"It will still be used after tamoxifen and aromatase inhibitors," said Dr. Di Leo.

Fulvestrant has been in use for 15 years, said Dr. Osborne. But its best days could be ahead, he suggested.

"It's been around for a long time but we don't believe it's been used optimally," said Dr. Osborne, adding that the suboptimal use was partly related to dose.

Dr. Osborne also noted that fulvestrant is "unique" among antiestrogens, because it can "destroy" the estrogen receptor.

"It can downregulate the estrogen receptor more intensively," he explained.

Pretreated With Antiestrogens and Recurring or Progressing

CONFIRM was a randomized double-blind parallel-group multicenter phase 3 study that compared the 2 doses of fulvestrant in postmenopausal women with estrogen-receptor-positive advanced disease recurring or progressing after previous endocrine therapy.

In total, 736 women (median age, 61.0 years) were recruited between 2005 and 2007 from 128 centers in 17 countries.

As mentioned, time to progression was statistically significantly longer for the patients receiving the 500 mg dose than for those receiving the 250 mg dose, corresponding to a 20% reduction in risk for progression (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68 - 0.94).

"We anticipate that the 500 mg regimen will become the established dose for fulvestrant," Dr. Di Leo told the meeting.

The treatment effect was consistent in the 6 predefined subgroups that were analyzed, said Dr. Di Leo.

The object response rate was similar for the 500 and 250 mg groups (9.1% vs 10.2%; odds ratio, 0.94; 95% CI, 0.57 - 1.55; P = .795). There was a numerical advantage in the clinical benefit rate for patients receiving the 500 mg dose, compared with those receiving the 250 mg dose (45.6% vs 39.6%; odds ratio, 1.28; 95% CI, 0.95 - 1.71; P = .1), but it was not statistically significant.

Also, there was a "trend" for improved overall survival for patients treated with the 500 mg dose, compared with those treated with the 250 mg dose (HR, 0.84; 95% CI, 0.69 - 1.03; P = .091), but the difference was not statistically significant, said Dr. Di Leo.

There was no difference in severity or the incidence of adverse events, noted Dr. Di Leo.

The investigators are currently conducting the Trans-CONFIRM study in an effort to understand whether the higher dose is mandatory in all patients or only in some.

Dr. Osborne reports being on the advisory board of Onyx Pharmaceuticals. Dr. Di Leo reports being on the advisory board and receiving funding from AstraZeneca.

32nd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract 25. Presented December 10, 2009.