Anastrozole Adjuvant ATAC Trial - Study of Anastrozole compared to NOLVADEX for Adjuvant Treatment of Early Breast Cancer – An anastrozole adjuvant trial was conducted in 9366 postmenopausal women with operable breast cancer who were randomized to receive adjuvant treatment with either anastrozole 1 mg daily, NOLVADEX 20 mg daily, or a combination of these two treatments for five years or until recurrence of the disease. At a median follow-up of 33 months, the combination of anastrozole and NOLVADEX did not demonstrate any efficacy benefit when compared with NOLVADEX therapy alone in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. Please refer to CLINICAL PHARMACOLOGY-Special Populations-Drug-Drug Interactions, PRECAUTIONS-Laboratory Tests, PRECAUTIONS-Drug Interactions and ADVERSE REACTIONS sections for safety information from this trial. Please refer to the full prescribing information for ARIMIDEX® (anastrozole) 1 mg Tablets for additional information on this trial.

Patients in the two monotherapy arms of the ATAC trial were treated for a median of 60 months (5 years) and followed for a median of 68 months. Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.87, 95% CI: 0.78, 0.97, p=0.0127] in the anastrazole arm compared to the NOLVADEX arm.

Node Positive - Individual Studies

Two studies (Hubay and NSABP B-09) demonstrated an improved disease-free survival following radical or modified radical mastectomy in postmenopausal women or women 50 years of age or older with surgically curable breast cancer with positive axillary nodes when NOLVADEX was added to adjuvant cytotoxic chemotherapy. In the Hubay study, NOLVADEX was added to &lequo;low-dose”CMF (cyclophosphamide, methotrexate and fluorouracil). In the NSABP B-09 study, NOLVADEX was added to melphalan [L-phenylalanine mustard (P)] and fluorouracil (F).

In the Hubay study, patients with a positive (more than 3 fmol) estrogen receptor were more likely to benefit. In the NSABP B-09 study in women age 50-59 years, only women with both estrogen and progesterone receptor levels 10 fmol or greater clearly benefited, while there was a nonstatistically significant trend toward adverse effect in women with both estrogen and progesterone receptor levels less than 10 fmol. In women age 60-70 years, there was a trend toward a beneficial effect of NOLVADEX without any clear relationship to estrogen or progesterone receptor status.

Three prospective studies (ECOG-1178, Toronto, NATO) using NOLVADEX adjuvantly as a single agent demonstrated an improved disease-free survival following total mastectomy and axillary dissection for postmenopausal women with positive axillary nodes compared to placebo/no treatment controls. The NATO study also demonstrated an overall survival benefit.

Node Negative - Individual Studies

NSABP B-14, a prospective, double-blind, randomized study, compared NOLVADEX to placebo in women with axillary node-negative, estrogen-receptor positive ( ≥ 10 fmol/mg cytosol protein) breast cancer (as adjuvant therapy, following total mastectomy and axillary dissection, or segmental resection<, axillary dissection, and breast radiation). After five years of treatment, there was a significant improvement in disease-free survival in women receiving NOLVADEX. This benefit was apparent both in women under age 50 and in women at or beyond age 50.

One additional randomized study (NATO) demonstrated improved disease-free survival for NOLVADEX compared to no adjuvant therapy following total mastectomy and axillary dissection in postmenopausal women with axillary node-negative breast cancer. In this study, the benefits of NOLVADEX appeared to be independent of estrogen receptor status.

Duration of Therapy

In the EBCTCG 1995 overview, the reduction in recurrence and mortality was greater in those studies that used tamoxifen for about 5 years than in those that used tamoxifen for a shorter period of therapy.

In the NSABP B-14 trial, in which patients were randomized to NOLVADEX 20 mg/day for 5 years vs. placebo and were disease-free at the end of this 5-year period were offered rerandomization to an additional 5 years of NOLVADEX or placebo. With 4 years of follow-up after this rerandomization, 92% of the women that received 5 years of NOLVADEX were alive and disease-free, compared to 86% of the women scheduled to receive 10 years of NOLVADEX (p=0.003). Overall survivals were 96% and 94%, respectively (p=0.08). Results of the B-14 study suggest that continuation of therapy beyond 5 years does not provide additional benefit.

Bookmark this page: