medwireNews: The phase 3 SALSA trial has demonstrated no benefit of extending aromatase inhibitor (AI) therapy by 5 years versus 2 years in postmenopausal women with hormone receptor-positive breast cancer who have already received 5 years of adjuvant endocrine therapy.
In addition, the longer duration of extended AI therapy “was associated with a greater risk of bone fracture,” report Michael Gnant, from the Medical University of Vienna in Austria, and co-investigators in The New England Journal of Medicine.
Writing in an accompanying editorial, Pamela Goodwin (University of Toronto, Ontario, Canada) notes that “[t]hese findings are consistent with those of two earlier trials” and “provide strong evidence against the routine use of more than 2 years of extended aromatase-inhibitor therapy in women who are at low or average risk, similar to those who were included in this trial.”
In the SALSA (ABCSG-16) study conducted at 75 centers in Austria, 3484 postmenopausal women with stage I–III disease who had received 5 years of adjuvant treatment with tamoxifen, AIs, or both sequentially were randomly assigned to receive anastrozole 1 mg/day for an additional 2 or 5 years.
Of the 3208 participants who remained in the trial without recurrence at 2 years and thus formed the primary analysis population, the majority had T1 (72.8%) and N0 (66.9%) breast cancers that had not required adjuvant chemotherapy (71.2%).
At 8 years after the completion of treatment in the 2-year group (ie, 10 years from randomization), the primary endpoint of disease-free survival in the primary analysis population was comparable in the 2- and 5-year groups, at rates of 73.6% and 73.9%, respectively (nonsignificant hazard ratio [HR]=0.99).
“A similar result was obtained after adjustment for potential confounding factors,” say Gnant and colleagues.
The overall survival rate at 8 years was likewise comparable between women who received an additional 2 or 5 years of anastrozole, at 87.5% versus 87.3% (nonsignificant HR=1.02).
And there were also no significant between-group differences with regard to the risk for contralateral breast cancer or second primary cancer.
However, the incidence of clinical bone fractures at 5 years after randomization was lower in the 2-year than 5-year treatment arm, at 4.7% versus 6.3% (HR=1.35), with the difference observed “despite the equivalent use of bone-targeted medications in the two groups,” point out the study authors.
They add that the “[s]ide effects of anastrozole were in line with the known toxicity profile of the drug.” Serious adverse events occurred in 26.5% of patients in the 2-year group and 40.2% of those in the 5-year group; the respective rates of events considered related to anastrozole were 2.3% and 4.0%.
The editorialist says in conclusion that “[d]ecisions regarding extended aromatase-inhibitor therapy will continue to be individualized with a combined assessment of recurrence risk, treatment tolerance, and patient preference.”
She continues: “The data provided by Gnant et al. in patients with hormone-receptor–positive breast cancer who are at low or average risk underscore the importance of avoiding iatrogenic complications when making these decisions.”
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N Engl J Med 2021; 385: 395–405
N Engl J Med 2021; 385: 462–463