Faslodex

SAN ANTONIO -- Fulvestrant, the first in a new class of drugs known as estrogen receptor downregulators, shows great promise for the treatment of breast cancer, oncologists asserted at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

In two new phase III AstraZenecasponsored clinical trials totalling 851 postmenopausal patients with advanced breast cancer that had progressed or recurred on tamoxifen therapy, fulvestrant (Faslodex) proved at least as effective as anastrozole (Arimidex), investigators reported.

"Fulvestrant will offer a new valuable treatment option in postmenopausal women with advanced breast cancer," declared Dr. C. Kent Osborne, principal investigator in the 400-patient North American trial.

Fulvestrant is the first pure anti-estrogen. Unlike tamoxifen and other selective estrogen receptor modulators, fulvestrant has no estrogen agonist activity, he said at the meeting.

Other hormonal therapies for breast cancer aim to block the estrogen receptor or lessen the amount of available estrogen in a patient's body; fulvestrant degrades the estrogen receptor, sometimes even causing it to disapper.

"For the moment, based upon these trials, I think it would be reasonable to use fulvestrant as second-line endocrine therapy if it were available today," commented Dr. Osborne, professor of medicine at Baylor College of Medicine, Houston.

However, exactly how best to use fulvestrant in advanced breast cancer will be determined over the next 2 years through ongoing or planned clinical trials.

One trial due to be reported next summer directly compares fulvestrant with tamoxifen as a first-line endocrine therapy in advanced breast cancer.

"The way we usually treat patients is that first they get, say, tamoxifen, and when that no longer works they get anastrozole, and when that no longer works they'll get another drug, a d then another. The question now s which sequence is the best. We need studies to determine whether anastrozole works after fulvestrant and fulvestrant works after tamoxifen," he explained at the meeting.

Dr. Osborne reported that the time to disease progression--the primary end point in the double-blind, multicenter North American trial--was 5.4 months with fulvestrant and 3.4 months with anastrozole, a nonsignificant difference.

More impressively, the median duration of response was 19.3 months with the estrogen receptor downregulator, compared with 10.5 months with the aromatase inhibitor. The drugs were equally well tolerated.

Dr. John F.R. Robertson reported that median time to disease progression, duration of response, and all other end points were virtually identical in the fulvestrant and anastrozole groups of the 451-patient, randomized but unblinded European phase III trial.

Again, both agents were well tolerated, added Dr. Robertson, professor of medicine at the University of Nottingham (England).

Far smaller earlier studies had suggested fulvestrant might have substantially greater clinical efficacy than current hormonal therapies for advanced breast cancer. Asked by an audience member whether the results of the phase III studies showing comparable efficacy for fulvestrant and anastrozole come as a disappointment in light of this more promising earlier work, Dr. Osborne replied, "Not really."

After all, there is today no curative treatment for advanced breast cancer. Fulvestrant's greatest potential application is not in metastatic disease, but in early breast cancer. This will be explored in future trials. The example of tamoxifen may be instructive, the oncologist continued.

"Tamoxifen doesn't cure anybody with advanced breast cancer, but it has significant survival benefit in the adjunct situation. Drugs that are just a little bit better than tamoxifen [such as anastrozole or fulvestrant] could presumably result in a lot more improvement when used in the adjunct situation than we're seeing in these metastatic trials," Dr. Osborne said at the meeting.

AstraZeneca filed a new drug application with the Food and Drug Administration in March requesting priority review of fulvestrant for the treatment of locally advanced or metastatic breast cancer in postmenopausal women who have previously progressed following hormonal therapy.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group