Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial.

Abstract

BACKGROUND:

The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds.

METHODS:

We analysed postmenopausal women (mean age 64 years [SD 9]) with localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen (n=3116). Efficacy measures, including death and risk-benefit indices, were analysed by intention to treat. Safety analyses were based on treatment first received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk-benefit analysis using the two global indices for the Women's Health Initiative and for Disease-Free Survival and Serious Adverse Events. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.

FINDINGS:

At median follow-up of 68 months (range 1-93), treatment-related adverse events occurred significantly less often with anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients given anastrozole had significantly fewer overall events for the Global Index of the Women's Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI 0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004).

INTERPRETATION:

Anastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events. Furthermore, it has a more favourable overall risk-benefit profile and lower recurrence rate than tamoxifen.

• Authors: Arimidex, Tamoxifen, Alone or in Combination Trialists' Group, A Buzdar, A Howell, J Cuzick, C Wale, W Distler, G Hoctin-Boes, J Houghton, G Y Locker, J M Nabholtz
• Journal: The Lancet. Oncology (Lancet Oncol) Vol. 7 Issue 8 Pg. 633-43 (Aug 2006) ISSN: 1470-2045 [Print] England
• PMID: 16887480 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Nitriles
• Triazoles
• Tamoxifen
• Anastrozole

Topics

• Anastrozole
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Drug Therapy, Combination
• Drug Tolerance
• Female
• Follow-Up Studies
• Humans
• Middle Aged
• Nitriles (administration & dosage, adverse effects)
• Postmenopause
• Risk Assessment
• Tamoxifen (administration & dosage, adverse effects)
• Triazoles (administration & dosage, adverse effects)