HOUSTON--A survival update of two mature phase III trials shows that
postmenopausal women with advanced breast cancer who received
anastrozole (Arimidex) after failing therapy with tamoxifen
(Nolvadex) survived significantly longer than those given megestrol
acetate (Megace). In addition, patients treated with anastrozole had
fewer side effects.
Aman Buzdar, MD, professor of breast medical oncology, University of
Texas M.D. Anderson Cancer Center, and his colleagues reported the
survival results, with a median of 31 months of follow-up, in the
September 15, 1998, issue of Cancer.
Two Parallel-Group Studies
The two randomized, parallel-group, multicenter studies--a North
American study led by Dr. Buzdar and a study from Europe, South
Africa, and Australia--were identical in design, allowing the data to
be combined for analysis. A total of 764 patients were randomized to
receive anastrozole at two different doses, 1 mg daily and 10 mg
daily, or megestrol, 40 mg four times daily.
At the time of data cut off, Dr. Buzdar reported, 473 patients had
been followed until death--151 in each of the two anastrozole groups
and 171 in the megestrol group. The estimated 2-year survival rates
from the combined analysis were 56%, 54%, and 46% for patients
receiving anastrozole 1 mg/d, anastrozole 10 mg/d, and megestrol,
Hazard ratios indicated a significant survival benefit for 1 mg
anastrozole, compared with megestrol (HR = 0.78), indicating
"that patients on anastrozole 1 mg are 22% less likely to die
over a given time period than are patients on megestrol acetate,"
Dr. Buzdar said. The 10-mg anastrozole dose showed a trend toward a
survival benefit over megestrol.
Significant Survival Advantage
Both anastrozole 1 mg and 10 mg showed an advantage in estimated
median time to death (26.7 and 25.5 months, respectively), compared
with megestrol (22.5 months). The anastrozole 1 mg dose provided a
significant survival advantage of 4.2 months. "It is likely that
the differences between the 1 and 10 mg anas-trozole doses were due
to the variability that may be inherent to clinical trials involving
advanced breast carcinoma patients," Dr. Buzdar said.
The 12-month safety analysis showed that all three treatments were
generally well tolerated. Megestrol was withdrawn from 10 patients
because of adverse drug reactions, compared with five patients and
seven patients for anastrozole 1 mg and 10 mg, respectively. There
were no treatment-related deaths with anastrozole whereas two
possible treatment-related deaths occurred with megestrol.
Dyspnea, hypertension, sweating, vaginal hemorrhage, weight gain, and
increased appetite were all reported two or more times more often
with megestrol than with anastrozole. Transient diarrhea occurred
more often with anastrozole.
"These data represent the first reported significant survival
advantage for an aromatase inhibitor compared with another endocrine
agent," Dr. Buzdar said. "The large size of the trials and
the strict response and statistical criteria employed add weight to
the significance of this finding," he added.
Studies currently in progress are directly comparing anastrozole with
tam-oxifen, both as first-line treatment for advanced disease and as
adjuvant treatment for early-stage breast cancer.