SAN ANTONIOFulvestrant (Faslodex), an
estrogen-receptor (ER) downregulator (see Figure), appears to be at
least as good as the aromatase inhibitor anastrozole (Arimidex) as second-line
therapy in postmenopausal women with advanced breast cancer who had progressed
or recurred on prior endocrine therapy.
The preliminary results of two phase III clinical trials
comparing the two agents were presented at the 23rd Annual San Antonio Breast
Cancer Symposium. Based on these trial results, AstraZeneca, manufacturer of
fulvestrant, has submitted a new drug application to the FDA requesting
priority review for this indication.
In the North American trial, the median duration of response in
the ful-vestrant arm was 19.3 months, compared with 10.5 months in the
anastrozole arm. Patients were followed for a median of 16.8 months.
In the European study, the median duration of response in the
two arms was almost identical, with 434 days (14.5 months) for fulvestrant and
425 days (14.2 months) for anastrozole. Patients were followed for a median of
305 days (10.2 months).
"Faslodex is the first antiestrogen with significant
clinical benefit in tamoxifen-resistant advanced breast cancer," said
J.F.R. Robertson, MD, of City Hospital, Nottingham, UK. "It is at least as
effective as Arimidex."
Dr. Robertson presented the findings of the European study on
behalf of the scheduled speaker, Anthony Howell, MD, who could not be present.
"It is a new treatment option for postmenopausal women with advanced
breast cancer," Dr. Robertson said.
Fulvestrant is a pure antiestrogen, the first in a new class of
antiestrogens that works by targeting and degrading the estrogen receptor
rather than blocking it
as with tamoxifen (Nolvadex).
The two studies had a similar design. Both were multicenter,
randomized trials. Patients in both received either 250 mg of fulvestrant
intramuscularly once monthly or 1 mg of anastrozole daily. The primary
distinction between the studies was that the North American study was a
double-blind, double-dummy study while the European study was not blinded.
There were also some slight differences in patient characteristics between the two studies. The North American
study included more ER-positive patients. The American patients were also 5 to
10 lb heavier than the European patients.
In the North American study, 400 patients were recruited
between May 1997 and August 1999. Since this was a double-dummy trial, women in
the anastrozole arm also received placebo injections while women in the
fulvestrant arm also received placebo pills.
In addition to the 9-month advantage in duration of response
that fulvestrant demonstrated in this trial, the median time to progression was
slightly longer with fulvestrant5.4 months and 3.4 months in the fulvestrant
and anastrozole arms, respectively (not significant).
An evaluation of deterioration in quality of life, an
"important but difficult endpoint," showed no statistically
significant differences between the two arms, said C. Kent Osborne, MD. Dr.
Osborne presented the results of the North American trial on behalf of the
North American Faslodex Investigator Group, Baylor College of Medicine,
"Faslodex is as effective as Arimidex for primary and
secondary endpoints," Dr. Osborne said. "It is active in
tamoxifen-resistant patients, as predicted."
In the European study, 451 patients were recruited between June
1997 and September 1999 and randomized to receive either fulvestrant (n = 222)
or anastrozole (n = 229). The median time to progression was similar in both
groups167 days (5.6 months) and 156 days (5.2 months) for fulvestrant and
Both treatments were well tolerated. In the North American
trial, 2.5% of fulvestrant patients and 2.6% of anastrozole patients withdrew
due to adverse events, Dr. Osborne said. Side effects for fulvestrant and
anastrozole, respectively, included the following: hot flushes,
23.5% and 24.9%; gastrointestinal disturbances, 56% and 56.2%; weight gain,
1.5% and 1.6%; and vaginitis, 3.4% and 2.6%. The European investigators
reported similar toxicity results.