In a phase III trial reported in The New England Journal of Medicine, Michael Gnant, MD, and colleagues found no difference in disease-free survival with 2 vs 5 years of treatment with the aromatase inhibitor anastrozole in postmenopausal women with early hormone receptor (HR)-positive breast cancer who had received 5 years of adjuvant endocrine therapy.
Michael Gnant, MD
The multicenter trial included 3,470 eligible women (intention-to-treat [ITT] population) who had received 5 years (± 12 months) of adjuvant endocrine therapy with tamoxifen, aromatase inhibitors, or both sequentially up until 12 months prior to random assignment. They were randomly assigned between February 2004 and June 2010 to receive 2 years (n = 1,732) or 5 years (n = 1,738) of anastrozole at 1 mg/d.
The primary endpoint was disease-free survival in the primary analysis set of patients, including all patients still participating in the trial with no recurrence at 2 years after random assignment (when treatment in the 2-year group had ended).
Median follow-up from random assignment was 118.0 months (interquartile range = 97.8–121.1 months). Recurrence within the first 2 years was observed in 62 patients in the 2-year group and 65 in the 5-year group.
The primary analysis set consisted of 3,208 patients, including 1,603 in the 2-year group vs 1,605 in the 5-year group. Among these patients, disease-free survival events had occurred in 335 patients in each group at 8 years after the end of treatment in the 2-year group (10 years after random assignment).
Disease-free survival rates were 73.6% in the 2-year group vs 73.9% in the 5-year group (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.85–1.15, P = 0.90). After adjustment for potential confounding factors, the hazard ratio was 1.00 (95% CI = 0.86–1.16).
In the primary analysis set, contralateral breast cancer occurred in 2.2% vs 2.1% of patients (HR = 1.15, 95% CI = 0.75–1.77). A second primary cancer occurred in 6.2% vs 6.7% (HR = 1.06, 95% CI = 0.81–1.38). Local recurrence occurred in 3.0% vs 2.4%, distant recurrence in 5.1% vs 4.9%, and death without recurrence in 4.4% vs 5.0%.
Among 1,665 vs 1,670 patients remaining in the study after 2 years, 8-year overall survival rates were 87.5% vs 87.3% (HR = 1.02, 95% CI = 0.83–1.25). The risk of clinical bone fracture between 2 and 5 years after random assignment was 4.7% vs 6.3% (HR = 1.35, 95% CI = 1.00–1.84).
Adverse events were consistent with the known toxicity profile of anastrozole. In the ITT population, serious adverse events occurred in 26.5% of patients in the 2-year group and 40.2% of those in the 5-year group; they were considered related to anastrozole in 2.3% vs 4.0%. The most common serious adverse event was osteoarthritis (1.7% vs 4.3%).
The investigators concluded, “In postmenopausal women with HR-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture.”
Disclosure: The study was funded by the Austrian Breast and Colorectal Cancer Study Group and AstraZeneca. For full disclosures of the study authors, visit nejm.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.