As reported in the Journal of Clinical Oncology by Olivia Pagani, MD, and colleagues, 13-year follow-up in a combined analysis of the phase III TEXT and SOFT trials has shown continued disease-free survival and distant recurrence–free interval benefit—but no overall survival benefit—with exemestane plus ovarian function suppression (OFS) vs tamoxifen plus OFS in premenopausal patients with estrogen/progesterone receptor–positive breast cancer. A “clinically significant” overall survival benefit appeared to be observed with exemestane/OFS in some patient subgroups.
Study Details
The combined analysis of SOFT and TEXT compared outcomes in 4,690 premenopausal women randomly assigned between November 2003 and April 2011 to 5 years of exemestane plus OFS or tamoxifen plus OFS.
Olivia Pagani, MD
In the most recent previous analysis, after a median follow-up of 9 years, exemestane/OFS maintained significantly improved disease-free survival (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.67–0.90) and distant recurrence–free interval but not overall survival (HR = 0.98, 95% CI = 0.79–1.22).
The current report details outcomes in the intent-to-treat population after a median follow-up of 13 years.
Key Findings
Disease-free survival rates at 12 years were 80.5% with exemestane/OFS vs 75.9% with tamoxifen/OFS (absolute improvement = 4.6%, 95% CI = 2.0%–7.2%; HR = 0.79, 95% CI = 0.70–0.90).
Proportions of patients free of distant recurrence at 12 years were 88.4% vs 86.6% (absolute improvement = 1.8%, 95% CI = –0.3% to 3.8%; HR = 0.83, 95% CI = 0.70–0.98, P = .03).
Overall survival at 12 years was 90.1% vs 89.1% (HR = 0.93, 95% CI = 0.78–1.11). Hazard ratios were 1.34 (95% CI = 0.98–1.84) during years 0 to 5, 0.72 (95% CI = 0.54–0.95) during years 5 to 10, and 0.88 (95% CI = 0.61–1.28) at ≥ 10 years.
Among patients with HER2-negative disease (86.0% of population), 12-year overall survival was 90.8% vs 88.8% (absolute 2% improvement; HR = 0.85, 95% CI = 0.70–1.04). Among HER2-negative patients who received chemotherapy (53.3% of the HER2-negative population), exemestane/OFS was associated with an absolute improvement of 3.3% in both the SOFT cohort (84.4% vs 81.1%) and the TEXT cohort (86.8% vs 83.5%).
The greatest absolute improvements in 12-year overall survival with exemestane/OFS vs tamoxifen/OFS were observed among patients at higher risk of relapse: patients aged < 35 years (81.6% vs 77.6%, absolute 4.0% improvement, 95% CI = –5.0% to 12.9); those with tumors > 2 cm (83.8% vs 79.3%, absolute 4.5% improvement, 95% CI = 0.1%–8.9%), and those with grade 3 tumors (83.6% vs 78.1%, 5.5% absolute improvement, 95% CI = –0.1% to 11.1%).
The investigators concluded, “These sustained reductions of the risk of recurrence with adjuvant exemestane plus OFS, compared with tamoxifen plus OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS.”
Olivia Pagani, MD, of Riviera-Chablais Hospital, Rennaz, Switzerland, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Frontier Science Foundation, Swiss Group for Clinical Cancer Research Switzerland, U.S. National Cancer Institute, Pfizer, Ipsen, Debiopharm, TerSera, AstraZeneca, and others. For full disclosures of the study authors, visit ascopubs.org.
