EDMONTON, CanadaIn what Jean-Marc Nabholtz, MD, calls the
first trials challenging tamoxifen as the primary drug of choice in
postmenopausal women with advanced breast cancer, anastrozole
(Arimidex, a nonsteroidal aromatase inhibitor) proved as effective as
tamoxifen (Nolvadex). Dr. Nabholtz, of the University of Alberta,
Edmonton, Canada, reported the results at the San Antonio Breast
Trial 0030, conducted at 97 centers in the United States and Canada,
included 353 postmenopausal patients with advanced breast cancers
that were ER and/or PR positive (90% of patients) or hormone status
unknown. Patients were randomized to receive1 mg/d of anastrozole or
20 mg/d of tamoxifen. Patients were treated until disease
This trial was a follow-up to trial 0027, conducted at 83 centers in
Europe and the rest of the world, which included 668 patients. The
two trials were designed to allow analysis of the combined data.
A major difference in the two trials was the greater number of
patients with receptor status unknown in the European trial. In
the European trial, the population was far from being a pure
population of patients known to be sensitive to endocrine
therapy, Dr. Nabholtz said, since about 55% of the patients had
unknown receptor status.
In trial 0030, the number of patients with prior adjuvant therapy was
about the same (40% in both arms) as was the number who had received
prior adjuvant endocrine therapy (about 20%). In terms of the extent
of metastatic disease, the only difference between the two groups was
in soft tissue presentation: 10.5% in the anastrozole group vs 18% in
the tamoxifen group, Dr. Nabholtz said. Both groups had extensive
visceral presentation: about 48%. In the European trial, fewer
patients had visceral disease (about 30%).
The objective response rates in the North American trial were 21.1%
for anastrozole vs 17% for tamoxifen. When adding stable disease of
at least 24 weeks, which has now emerged as an important
concept in the assessment of hormonal therapy benefits, Dr.
Nabholtz said, a significant clinical benefit was observed in favor
of anastrozole (59% vs 46% for tamoxifen) (P = .0098).
The rate of disease progression was 67% with anastrozole vs 76% with
tamoxifen, and median time to progression was 11.1 months for
anastrozole vs 5.6 months for tamoxifen (P = .005).
When the data from the two trials were combined, the objective
response rate was 29% for anastrozole vs 27.1% for tamoxifen.
Clinical benefit was 57.1% for anastrozole vs 52% for tamoxifen.
The rate of disease progression was 71% in the anastrozole patients
and 76% with tamoxifen; median time to progression was 8.5 months for
anastrozole and 7 months for tamoxifen.
The numerical advantage for anastrozole with respect to time to
progression in the combined analysis was not significant when all
patients were included (P = .103) but did prove significant when only
patients known to be receptor positive were included in the analysis
(P = .022).
Both drugs were well tolerated, with fewer thromboembolitic episodes
in the anastrozole patients (7.6% vs 4.5%, although this was not
significant) and fewer vaginal bleeding problems with anastrozole.
Dr. Nabholtzs team concluded from these two large trials that
anastrozole is at least as effective as tamoxifen as first-line
treatment of advanced breast cancer in postmenopausal women.
There is a suggestion of an efficacy benefit for anastrozole
over tamoxifen in receptor-positive patients, he said, and
these data, along with the good tolerability shown by patients on
anastrozole, argue that this drug should be considered as an
alternative to tamoxifen in the first-line treatment of advanced
breast cancer in postmenopausal women.
Finally, Dr. Nabholtz urged that phase III clinical trials involving
hormonal therapy should exclude patients with unknown hormone
receptors and try to prove the concept with patients known to be
sensitive to hormonal therapy.