Among the women, 27% were younger than 40 years, 42% were lymph node–positive, 36% had a tumor sized larger than 2 cm, and 12% were HER2-positive. Median time from surgery to randomization was 1.6 months.
Dr. Pagani said that due to low event rates, in 2011 the protocol was amended to enable the aromatase inhibitor question (exemestane vs. tamoxifen plus OFS) to be answered by a joint analysis of the TEXT and SOFT trials. Also determined was the value of OFS in women who remain premenopausal and are suitable for adjuvant tamoxifen.
At a median follow-up of 5.7 years, 514 (11%) DFS events were reported in the intent-to-treat population comparing exemestane plus OFS (n = 2,346) versus tamoxifen plus OFS (n = 2,344).
“Patients assigned exemestane plus OFS had significantly reduced DFS hazard (hazard ratio [HR], 0.72; 95% CI: 0.60-0.85; P = 0.0002) versus tamoxifen plus OFS,” Dr. Pagani said. Five-year DFS was 91.1% in the exemestane-plus-OFS group compared with 87.3% in the tamoxifen-plus-OFS group.
Reductions were similar for the secondary endpoints of 5-year breast cancer–free interval: 92.8% versus 88.8%, respectively (HR, 0.66; 95% CI: 0.55-0.80, P < 0.0001), and distant recurrence-free interval, 93.8% versus 92.0% (HR, 0.78; 95% CI: 0.62-0.97, P = 0.02). A total of 60% of first failures involved distant sites, she said. The absolute improvement with exemestane plus OFS 5-year freedom from breast cancer was 5.5% in TEXT and 3.9% in SOFT.
The 5-year overall survival rates were high in both groups: 96.9% in the exemestane plus OFS group and 95.9% in the tamoxifen plus OFS group.
Adverse event (AE) profiles were comparable with postmenopausal women; the incidence of targeted grade 3/4 AEs were similar, 31% of the women in the exemestane plus OFS group and 29% of the tamoxifen plus OFS group. Most commonly observed AEs in both groups were depression, hypertension, and hot flushes/flashes. Exemestane plus OFS caused more musculoskeletal, osteoporosis, and fracture AEs as well as vaginal dryness, decrease in libido, and dyspareunia, while tamoxifen-plus-OFS patients had higher rates of thrombosis/embolism, hot flushes/flashes, sweating, and urinary incontinence.
Early cessation of all assigned treatments was more frequent with exemestane plus OFS, 16%, versus 11% for tamoxifen plus exemestane, Dr. Pagani reported. Patients self-reported differential effects, but overall quality of life did not favor either treatment.
Currently, standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen. In high-risk younger women, physicians in some countries recommend adding OFS to tamoxifen, an approach less common in the United States.
No significant difference in overall survival (OS) was observed; however, data remain premature at this early point in the follow-up of HR-positive breast cancer. Long-term follow-up is needed to assess accurately the impact of these two treatments on long-term survival.
Results were published online in the New England Journal of Medicine at the conclusion of Dr. Pagani’s presentation.
- Pagani O, Regan MM, Walley B et al. Abstract LBA1. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.