Anastrozole after 2 years of tamoxifen demonstrates survival benefit

Postmenopausal women with hormone-sensitive early-stage breast cancer who have received at least 2 years of adjuvant treatment with tamoxifen can benefit in overall survival from a switch to anastrozole, according to the results of a meta-analysis published in the journal Lancet.

This finding is supported by earlier recommendations from the American Society of Clinical Oncology (ASCO), which in 2004 stated that a treatment duration of 5 years with only tamoxifen was not the ideal supplementary therapy for hormone-sensitive early-stage breast cancer. The group advised that therapy should also incorporate use of an aromatase inhibitor in an effort to limit tumor reappearance.

In this study, researchers analyzed 3 clinical trials from January 1, 2004, to March 31, 2005: The Austrian Breast and Colorectal Cancer Study Group (ABCSG 8) (n=2579), Arimidex-Nolvadex (ARNO 95)(n=979), and the Italian Tamoxifen Anastrozole (ITA) (n=448) studies. Only phase 3 trials involving women with histologically confirmed hormone-positive early-stage breast cancer were considered for inclusion in the study. These women (N=4,006) were treated with either a third-generation aromatase inhibitor or continued tamoxifen after 2–3 years of adjuvant tamoxifen. Data were reviewed via a stratified Cox proportional hazards model; covariates included age, tumor size, nodal status, grade, surgery, and chemotherapy.

Median follow-ups for each study were: ABCSG 8, 24.4 months (range: 0–84.4); ARNO 95, 32.7 months (range: 0–89.5); and ITA, 50.4 months (range: 0–79.8). Overall, meta-analysis median follow-up was 30 months (range: 0–89.5). There was a total duration of follow-up of 5,339 person-years for the tamoxifen group and 5,389 person-years for the anastrozole group.

Primary end points were all related to survival: disease-free survival, event-free survival, distant-recurrence-free survival, and overall survival.

The likelihood of disease return and number of deaths were significantly reduced in patients who switched to anastrozole compared with patients who continued tamoxifen.(92 vs 159 and 66 vs 90, respectively). The reductions represented marked improvement in disease-free survival (HR=0.59; 95% CI, 0.48–0.74; P<.0001); event-free survival (HR=0.55; 95% CI, 0.42–0.71; P<.0001); distant recurrence-free survival (HR=0.61; 95% CI, 0.45–0.83; P=.002); and overall survival (HR=0.71; 95% CI, 0.52–0.98; P=.04).

The authors said the advantage of switching to anastozole versus continued tamoxifen remained regardless of nodal status, tumor size, or whether chemotherapy was used.

Each of the studies showed an anastrozole benefit, but a prognosis difference in the ABSCG 8 trial resulted in more deaths without recurrence, and a hazard ratio near 1.00. The authors added that there were fewer deaths (due to breast cancer and non-breast-cancer causes) in the anastrozole group compared with the tamoxifen group in the ABSCG8 trial.

Despite the demonstrated benefits of anastrozole treatment after 2 years of tamoxifen compared with continued tamoxifen, the authors said more research is needed before recommending aromatase inhibitors as initial adjuvant treatment, or as treatment after 2-plus years of tamoxifen. Evidence remains uncertain, according to the authors, and real data from well-designed clinical trials are warranted for such treatment strategies.

However, the authors said enough evidence does exist to consider switching postmenopausal women from adjuvant tamoxifen to anastrozole after 2–3 years.

SOURCE Jonat W, Gnant M, Boccardo F, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: A meta-analysis. Lancet. 2006;7:991–996.