SAN ANTONIOFor postmenopausal women with
hormone-receptor-positive early-stage breast cancer, switching to anastrozole
(Arimidex) after 2 years of tamoxifen is more effective than continuing on
tamoxifen, according to Raimund Jakesz, MD, Vienna Medical School, Vienna,
Austria. The conclusion arose out of analysis of combined results of two
trials enrolling a total of 3,224 women: the Viennese ABCSG (Austrian Breast
and Colorectal Cancer Study Group) Trial 8, and the German ARNO 95 Trial (by
the German Adjuvant Breast Cancer Group).
The ABCSG and ARNO trials were nearly identical, Dr. Jakesz
said at the 27th Annual San Antonio Breast Cancer Symposium (abstract 2). They
included primarily favorable prognostic groups (T1 70%, node negative 74%,
grade 1-2 95%). The main difference was that the ABCSG trial allowed grade 1-2
tumors, while ARNO also included grade 3 tumors. Nearly 40% were less than 60
years old. About 81% were both estrogen-receptor and progesterone-receptor
positive. Breast conservation was possible in approximately 77%. No patients
In both trials, patients were randomized to 3 years of
tamoxifen (n = 1,606) or anastrozole (n = 1,618) after 2 years of tamoxifen.
The primary endpoint was event-free survival, with events defined as
locoregional recurrences, distant metastases, or contralateral breast cancer.
In this interim analysis, event-free survival significantly
favored anastrozole (see Table), with a 40% risk reduction. The finding met the
stopping boundary for event-free survival, and no further patients are being
recruited into the two studies. An analysis of variables affecting event-free
survival showed anastrozole to be an independent prognostic factor, along with
negative nodal status and non-grade 3 tumor grade.
Dr. Jakesz noted that unlike other trials, the major
difference in events between tamoxifen and anastrozole was in distant
recurrences, with 75 such events in the tamoxifen group and 46 in the
anastrozole group, resulting in a significant difference in
distant-recurrence-free survival favoring anastrozole (HR = 0.61, P =
.0067). There was no overall survival benefit for anastrozole, which Dr. Jakesz
attributed to the low number of deaths and the short follow-up period.
Overall, both treatments were well tolerated. As expected,
there were significantly more fractures in patients switching to anastrozole27
(2.4%) vs 14 (1.2%) for tamoxifen. Dr. Jakesz pointed out that because
gynecological side effects generally occur soon after initiating tamoxifen
therapy, there were no differences between groups in this respect.
Based on both event-free and distant-recurrence-free
survival, the superior strategy, Dr. Jakesz concluded, is to switch women from
tamoxifen to anastrozole at 2 years. Studies are needed to determine whether
initial adjuvant anastrozole given for 5 years is superior to switching from tamoxifen to anastrozole after 2 years. He noted
that ABCSG-16 (SALSA) is evaluating 2 vs 5 years of anastrozole following 3
years of tamoxifen therapy.