medwireNews: Extended use of anastrozole beyond 5 years of sequential adjuvant therapy does not significantly prolong disease-free survival (DFS) in the majority of postmenopausal women with hormone receptor-positive early breast cancer, Dutch researchers report.
They say: “We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy [in these patients].”
For the phase III DATA trial, Vivianne Tjan-Heijnen, from Maastricht University Medical Center, and co-investigators randomly assigned 1912 postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2–3 years of adjuvant tamoxifen to receive either 3 or 6 years of oral anastrozole 1 mg daily.
At 3 years post randomization, 833 patients in the 3-year anastrazole group, and 827 in the 6-year group were disease-free. These patients were followed-up for a further median 4.2 years, during which time 145 and 116 in the 3- and 6-year groups, respectively, experienced disease progression or death.
As reported in The Lancet Oncology, the 5-year adapted DFS rate, beginning 3 years after randomization, was 79.4% in the 3-year group and 83.1% in the 6-year group, a difference that was not statistically significant.
There was also no significant difference between the 3-year and 6-year anastrazole groups in 5-year adapted overall survival rates, at 90.4% versus 90.8%.
In addition to a lack of difference in survival between the two groups, the researchers found that extended anastrazole use was associated with increased rates of adverse events including all-grade arthralgia or myalgia (58% of 827 in the 6-year treatment group vs 53% of 833 in the 3-year treatment group) and osteopenia or osteoporosis (21 vs 16%).
However, post-hoc exploratory subgroup analyses, which Tjan-Heijnen et al emphasize should be interpreted with caution, suggested that extended anastrazole treatment may be associated with significantly improved 5-year adapted DFS irrespective of chemotherapy use in patients with node-positive, estrogen and progesterone receptor-positive disease, at a hazard ratio of 0.64 in favor of the 6-year group. This hazard ratio fell further, to 0.53, in patients that also had large (≥T2) tumors.
The authors conclude that when their findings are taken together with those of two similar trials – NSABP-B42 and IDEAL – “benefit might be seen from extended use of aromatase inhibitors in subgroups of patients who were initially treated with tamoxifen.”
They add: “Any benefit, however, comes at a price; shown by the continuous decline in treatment compliance over time in all three new trials.
“Hence, careful assessment of potential benefits and risks is required before recommending extended aromatase inhibitor therapy.”
In a comment that accompanies the research, Kathleen Pritchard, from the University of Toronto in Ontario, Canada, says the study “adds considerably to the body of data examining the important question of optimal duration of adjuvant endocrine therapy.”
But she warns against “extrapolating clinical conclusions from underpowered subset analyses.”
Pritchard concludes: “It is to be hoped that when the results of additional studies of similar design to DATA […] become available, comparisons between studies and appropriate meta-analyses might help to more accurately identify any robust predictive factors that will help us to personalise these therapies.”
By Laura Cowen
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