Because of the significant risk for recurrence in hormone receptor (HR)-positive breast cancer, extended adjuvant endocrine therapy has been of interest to determine whether it may improve outcomes in these patients. At the 2016 San Antonio Breast Cancer Symposium (SABCS), separate clinical trials of extended aromatase inhibitor (AI) therapy were presented, the results of which do not support extended therapy for all postmenopausal women with HR-positive breast cancer.
Vivianne Tjan-Heijnen, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, the Netherlands, presented findings from the multicenter, phase 3 DATA study, in which 1912 postmenopausal women with HR-positive breast cancer were randomized to 3 or 6 years of adjuvant anastrozole after 2 to 3 years of adjuvant tamoxifen.
Extended anastrozole therapy did not lead to an advantage in 5-year adapted disease-free survival (DFS), which was the primary end point of the study. Adapted DFS was defined as the DFS starting as of 3 years after randomization. In the overall analysis, with a minimum of 6 years of follow-up after randomization, 5-year adapted DFS was 83.1% in patients randomized to 6 years of anastrozole compared with 79.4% in those randomized to 3 years of anastrozole, for a hazard ratio of 0.79, which did not achieve statistical significance (P = .07).
Findings from the study did suggest benefits for a select group of patients—those with both estrogen receptor (ER)-positive and progesterone receptor (PR)-positive disease, HER2-negative disease, large tumor load, and previous chemotherapy.
In the subgroup of patients with disease that was ER- and PR-positive, HER2-negative, node-negative, and who had received neoadjuvant chemotherapy, the 5-year adapted DFS was 86% in those randomized to receive 6 years of adjuvant anastrozole compared with 75.9% in those randomized to receive 3 years of anastrozole (hazard ratio, 0.58; P = .01). The subgroup analysis was not prespecified, “but I think this is very useful for daily clinical practice,” Dr Tjan-Heijnen said.
Six years of anastrozole for patients with larger (pathologic tumor stage II or III/IV) tumors resulted in approximately 6% absolute improvement in adapted 5-year DFS, “which I think is also clinically meaningful,” she said. The findings favored 6 years of anastrozole in the node-positive group (hazard ratio, 0.72; 95% confidence interval [CI], 0.52-1.00), patients with both ER- and PR-positive disease (hazard ratio, 0.70; 95% CI, 0.53-0.92), patients with HER2-negative disease (hazard ratio, 0.79; 95% CI, 0.61-1.03), and those who received neoadjuvant chemotherapy (hazard ratio, 0.68; 85% CI, 0.49-0.92).
There was no difference in 5-year adapted overall survival (OS) in women receiving 6 years or 3 years of anastrozole: 90.8% versus 90.4%, respectively, although the median adapted follow-up was only 4.1 years at the time of the presentation.
There was a slightly higher rate of adverse events in the 6-year arm compared with the 3-year arm, including arthralgia/myalgia (57.6% vs 51.9%), bone fracture (9.8% vs 7.4%), osteopenia/osteoporosis (20.9% vs 16.5%), and cardiovascular events, including arrhythmia (13.4% vs 12.9%).
Approximately 80% of patients completed 3 years of adjuvant anastrozole, and 60% were able to complete 6 years.
Extended Letrozole Not Ideal
In the phase 3 IDEAL trial, 1824 postmenopausal women were randomized to either 2.5 or 5 years of letrozole therapy after initial therapy for 5 years with tamoxifen and/or AIs.
The 5-year DFS rate was 88.4% in patients receiving an additional 2.5 years of letrozole, and 87.9% in those receiving 5 additional years (hazard ratio, 0.96; P = .70), reported Erik Blok, MD, Department of Medical Oncology, Leiden University Medical Center, the Netherlands. Rates of OS were 93.5% and 92.6%, respectively (hazard ratio, 1.08; P = .59). A hazard ratio of 0.37 was observed in second primary breast cancers in favor of the 5-year extended therapy.
The investigators did not identify a subgroup that would benefit from the extended therapy of ≤10 years.
The occurrence of adverse events was high (70%) in the IDEAL trial, resulting in a high rate of nonadherence.
As reported in the April Breast Cancer Bulletin, a separate analysis (NSABP B-42), also presented at SABCS 2016, showed no improvement in DFS or OS among postmenopausal women with early-stage HR-positive breast cancer who were randomized to 5 years of letrozole (compared with placebo) following an initial 5 years of AI adjuvant therapy.