Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial

Lancet Oncology 2008; 9:45-53

Effect of anastrozole and tamoxifen as adjuvant treatment for early-
stage breast cancer: 100-month analysis of the ATAC trial

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists'
Group
‡Writing committee members listed at end of paper

Summary
Background
Little data exist on whether efficacy benefits or side-effects persist
after 5 years of adjuvant treatment with an aromatase inhibitor. We
aimed to study long-term outcomes in the Arimidex, Tamoxifen, Alone or
in Combination (ATAC) trial that compares anastrozole with tamoxifen
after a median follow-up of 100 months.

Methods
We analysed postmenopausal women with localised invasive breast
cancer. The primary endpoint disease-free survival (DFS), and the
secondary endpoints time to recurrence (TTR), incidence of new
contralateral breast cancer (CLBC), time to distant recurrence (TTDR),
overall survival (OS), and death after recurrence were assessed in the
total population (intention to treat; ITT: anastrozole, n=3125;
tamoxifen, n=3116; total 6241) and the hormone-receptor-positive
subpopulation, the clinically important subgroup for which endocrine
treatment is now known to be effective (84% of ITT: anastrozole,
n=2618; tamoxifen, n=2598; total 5216). After treatment completion,
fractures and serious adverse events continued to be collected blindly
(safety population: anastrozole, n=3092; tamoxifen, n=3094; total
6186). This study is registered as an International Standard
Randomised Controlled Trial, number ISRCTN18233230.

Findings
At a median follow-up of 100 months (range 0–126), DFS, TTR, TTDR, and
CLBC were improved significantly in the ITT and hormone-receptor-
positive populations. For hormone-receptor-positive patients: DFS
hazard ratio (HR) 0·85 (95% CI 0·76–0·94), p=0·003; TTR HR 0·76 (0·67–
0·87), p=0·0001; TTDR HR 0·84 (0·72–0·97), p=0·022; and CLBC HR 0·60
(0·42–0·85), p=0·004. Absolute differences in time to recurrence
increased over time (TTR 2·8% [anastrozole 9·7% vs tamoxifen 12·5%] at
5 years and 4·8% [anastrozole 17·0% vs tamoxifen 21·8%] at 9 years)
and recurrence rates remained significantly lower on anastrozole
compared with tamoxifen after treatment completion (HR 0·75 [0·61–
0·94], p=0·01). The fewer deaths after recurrence (anastrozole 245 vs
tamoxifen 269) was not significant (HR 0·90 [0·75–1·07], p=0·2), and
no effect was noted for OS (anastrozole 472 vs tamoxifen 477) HR 0·97
[0·86–1·11], p=0·7). Fracture rates were higher in patients receiving
anastrozole than in those receiving tamoxifen during active treatment
(number [annual rate]: 375 [2·93%] vs 234 [1·90%]; incidence rate
ratio [IRR] 1·55 [1·31–1·83], p<0·0001), but were not different after
treatment was completed (off treatment: 146 [1·56%] vs 143 [1·51%];
IRR 1·03 [0·81–1·31], p=0·79). We did not note any significant
difference in risk of cardiovascular morbidity or mortality between
anastrozole and tamoxifen treatment groups.

Interpretation
These data show long-term safety findings and establish clearly the
long-term efficacy of anastrozole compared with tamoxifen as initial
adjuvant treatment for postmenopausal women with hormone-sensitive,
early breast cancer, and provide statistically significant evidence of
a larger carryover effect after 5 years of adjuvant treatment with
anastrozole compared with tamoxifen.

Comment: http://www.thelancet.com/journals/lanonc/article/PIIS1470204507703923/fulltext

* * *
No difference in overall survival -- isn't that the bottom line?

Marilyn
.

Quantcast