Mature results from ABCSG-12: Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with endocrine-responsive early breast cancer.

BACKGROUND: The ABCSG-12 trial examined the efficacy of ovarian suppression using goserelin in combination with anastrozole (ANA) or tamoxifen (TAM) ± zoledronic acid (ZOL) in premenopausal patients (pts) with endocrine-responsive breast cancer (EBC). The first efficacy analysis at ASCO 2008, showed no difference between TAM and ANA, but adding ZOL significantly reduced the risk of disease-free survival (DFS) events by 36% (p = 0.01). Longer follow-up is now available. METHODS: 1,803 premenopausal pts with EBC were randomized to goserelin (3.6 mg q 28 d) and TAM (20 mg/d) or ANA (1 mg/d) ± ZOL (4 mg q 6 mo). Endpoints were DFS and overall survival (OS); both were analyzed using log-rank test and Cox models. Compared with 2008 data, we now report on 34% more DFS events and 55% more deaths, based on a December 1, 2009, data cutoff. RESULTS: With a median follow-up of 62 mo, 183 DFS events and 65 deaths were reported. Overall, ZOL reduced the risk of DFS events by 32% (HR = 0.68 [95% CI = 0.51, 0.91]; p = 0.009). The risk reduction by ZOL was identical in the TAM and ANA strata (HR = 0.68 [0.44, 1.05] for TAM, HR = 0.68 [0.45, 1.02] for ANA), and for N– and N+ pts. With respect to OS, ZOL reduced the risk of death by 34% (HR = 0.66 [0.41, 1.09]; 0 = 0.10). The OS benefit was even more pronounced in the N+ subgroup (HR = 0.61; p= NS). There was no difference in DFS between pts who received TAM alone vs ANA alone (HR = 1.11 [0.84, 1.50]; P = .44). However, ANA pts did worse with respect to OS (HR = 1.74 [1.05, 2.87]; p = 0.03) vs TAM, probably due to differences in post-relapse treatment. Treatments were generally well tolerated. There was no case of renal failure or osteonecrosis of the jaw (ONJ). CONCLUSIONS: With longer follow-up of ABCSG-12, the addition of ZOL (4 mg q 6 mo) consistently improves both DFS and OS in the ANA and TAM subgroups, and in N+ and N– pts. There was no DFS difference between ANA and TAM, but ANA pts had inferior OS vs TAM; probably because ANA pts lack palliative aromatase inhibitor treatment. Based on these results and the known anticancer activity of adjuvant ZOL, this treatment should be considered for premenopausal pts with EBC.