Worse Patient-Reported Outcomes With Addition of Ovarian Function Suppression to Tamoxifen in Premenopausal Women With Breast Cancer
In the phase III Eastern Cooperative Oncology Group (ECOG) E-3193 (Intergroup 0142) trial, reported in the Journal of Clinical Oncology by Tevaarwerk et al, adding ovarian function suppression to tamoxifen was associated with worse patient-reported outcomes in premenopausal women with node-negative, hormone receptor-positive breast cancer. The trial was closed early due to slow accrual, and did not meet enrollment targets for planned assessment of the primary endpoints of disease-free survival and overall survival.
Study Details
In the open-label trial, 345 premenopausal women with axillary node-negative, hormone receptor–positive breast cancer tumors ≤ 3 cm were randomly assigned between September 1994 and November 1997 to receive tamoxifen alone (n = 171) or tamoxifen plus ovarian function suppression (n = 174). No adjuvant chemotherapy was permitted.
Ovarian function suppression consisted of patient or physician choice of luteinizing hormone–releasing hormone analog (goserelin 3.6 mg depot every 4 weeks for 5 years, leuprolide acetate 3.75 mg every 4 weeks for 5 years), surgical ablation, or radiation ablation (20 Gy in 10 fractions). No dose reductions were permitted.
Patient-reported outcomes and health-related quality of life were assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B), questions from the Postmenopausal Estrogen/Progestin Intervention checklist, and the Sexual Activity Questionnaire.
The target enrollment for assessment of disease-free survival and overall survival was 1,600 patients. The actual accrual was large enough for the preplanned analysis of patient-reported outcomes.
Survival Outcomes
Median follow-up was 9.9 years. Five-year overall survival was 97.6% (95% confidence interval [CI] = 93.6%–99.1%) for tamoxifen plus suppression vs 95.2% (95% CI = 90.5%–97.6%) for tamoxifen alone (adjusted hazard ratio [HR] = 1.19, P = .67, for tamoxifen vs tamoxifen plus suppression).
Five-year disease-free survival was 89.7% (95% CI = 83.9%–93.5%) for tamoxifen plus suppression vs 87.9% (95% CI = 81.9%–92.0%) for tamoxifen alone (adjusted HR = 1.17, P = .62, for tamoxifen vs tamoxifen vs suppression).
Ten-year overall survival was 92.4% vs 92.5%, and 10-year disease-free survival was 87.1% vs 85.9%.
Adverse Events and Patient-Reported Outcomes
Grade 3 or 4 adverse events occurred in 22.4% of the tamoxifen plus suppression group vs 12.3% of the tamoxifen group (P = .004), with the most common being hot flashes (16.1% vs 4.7%) and weight gain (3.4% vs 2.3%).
Women receiving tamoxifen plus ovarian function suppression had more menopausal symptoms at 6 months and at 1, 2, 3, 4, and 5 years, with the differences being significant at 1, 2, and 3 years (all P < .05), and significantly reduced sexual function at every time point (all P < .05). Health-related quality of life was significantly poorer in this group at year 3 (P = .003). Differences in these outcomes tended to diminish over time, likely reflecting the increasing proportion of women receiving tamoxifen alone who reached menopause during follow-up.
The investigators concluded: “When added to tamoxifen, [ovarian function suppression] results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding [ovarian function suppression] to tamoxifen.”
Amye J. Tevaarwerk, MD, of University of Wisconsin, Madison, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the National Institutes of Health and National Cancer Institute. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
