That’s a question that has been vexing oncologists for more than a decade, but final results from a large study now suggest that, after an initial 5 years of adjuvant endocrine therapy with tamoxifen and/or an AI, an additional 5 years of AI therapy offer no clinical benefits, compared with an additional 2 years of therapy.
What’s more, 5 years of additional treatment were associated with a significantly increased risk for fractures, compared with 2 years of therapy, Michael Gnant, MD, from the Medical University of Vienna, and colleagues reported in the phase 3 Austrian Breast and Colorectal Cancer Study Group Trial 16 (ABCSG-16).
“Thus, in postmenopausal women with hormone receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy, the extension of aromatase inhibitor therapy for 2 years rather than 5 years was sufficient to maximize the benefits of such therapy in most patients without extending the exposure to toxic effects,” they concluded.
The study was published online on July 28, 2021, in the New England Journal of Medicine.
The new results “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,” Pamela J. Goodwin, MD, from the Lunenfeld–Tanenbaum Research Institute at the University of Toronto, wrote in an accompanying editorial.
She noted that these latest results echo those of two earlier studies: the DATA trial and the optimistically named IDEAL trial, both of which showed no benefit of short-term versus longer-term adjuvant endocrine therapy with regard to either disease-free survival (DFS) or overall survival (OS).
“These results 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,” Dr. Goodwin commented.
ABCSG-16 details
Dr. Gnant and colleagues enrolled 3,484 women aged 80 years or younger with HR-positive stage I, II, or III breast cancer for whom there was no evidence of recurrence at baseline. The patients had all received adjuvant tamoxifen or an AI for 5 years; for some patients, the two drugs were administered in sequence until 12 months before randomization.
The patients were randomly assigned to receive oral anastrozole 1 mg daily for either 2 or 5 additional years.
Among all patients, 3,208 had experienced no recurrence 2 years after randomization. These patients were included in the primary DFS analysis. Of this group, 1,635 (51%) had received tamoxifen alone for 5 years, 235 (7.3%) had received an AI alone, and 41.7% had received sequential AIs and tamoxifen.
At a median follow-up of 118 months after randomization, disease progression or death occurred in 670 women – 335 in each trial arm.
The rate of DFS 10 years after randomization was 73.6% in the 2-year additional-therapy group and 73.9% in the 5-year group. The hazard ratio for disease recurrence or death was 0.99 and was not significant. After adjustment for potential confounding factors, the HR remained essentially unchanged (HR, 1.0).
Overall survival at 8 years, a secondary endpoint, was virtually identical between the groups, at 87.5% in the 2-year group and 87.3% in the 5-year group. The HR for death from any cause was 1.02 and was not significant.
The HR for contralateral breast cancer was 1.15, and the HR for a second primary cancer was 1.06; neither was statistically significant.
Although the use of bone-targeted medication was similar between the groups, among patients in the 2-year group, the incidence of clinical bone fractures 5 years after randomization was lower, at 4.7% versus 6.3%, which translates to an HR for fracture with 5 additional years of AI therapy of 1.35 (95% confidence interval, 1.00-1.84).
Adverse events with anastrozole were consistent with its known toxicity profile. At least one serious adverse event occurred in 26.5% of patients in the 2-year group and in 40.2% in the 5-year group. Investigator-assessed serious adverse events that were judged to be related to anastrozole occurred in 2.3% and 4.0% of patients, respectively.
Osteoarthritis, the most frequently reported adverse event, was documented in 1.7% of patients in the 2-year group and in 4.3% in the 5-year group.