In a phase III trial reported in the Journal of Clinical Oncology, Kim et al found that the addition of 2 years of ovarian function suppression during ongoing tamoxifen treatment improved disease-free survival vs 5 years of tamoxifen alone in patients with estrogen receptor–positive breast cancer who remained in a premenopausal state or resumed ovarian function after chemotherapy.
Study Details
“The addition of 2 years of ovarian function suppression to [tamoxifen] significantly improved [disease-free survival] compared with [tamoxifen] alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.”— Kim et al
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The open-label, multicenter trial enrolled 1,370 patients between March 2009 and March 2014. A total of 1,282 evaluable patients (intent-to-treat population) were randomly assigned to receive either tamoxifen plus ovarian function suppression (n = 635) or tamoxifen alone (n = 647). Patients were aged ≤ 45 years and had undergone definitive surgery and completed neoadjuvant or adjuvant chemotherapy.
All patients received 5 years of tamoxifen 20 mg/d starting at enrollment. When ovarian function—assessed every 6 months for 2 years from enrollment—was confirmed to be premenopausal, the patient was randomly assigned to continue tamoxifen alone or to receive 2 years of ovarian function suppression consisting of goserelin given via 3.6-mg subcutaneous injection every 28 days during ongoing tamoxifen.
The primary endpoint was disease-free survival, defined as duration from time of enrollment to time of the first event.
Disease-Free Survival
Overall, among 1,370 initially enrolled patients, 155 (11.3%) remained premenopausal at the time of enrollment; 745 (54.4%) resumed ovarian function within 6 months of completing chemotherapy; 381 (27.9%) resumed ovarian function between 6 and 24 months after chemotherapy; and 88 (6.4%) had chemotherapy-induced amenorrhea for 2 years after enrollment.
KEY POINTS
- The addition of ovarian function suppression to tamoxifen was associated with prolonged disease-free survival.
- Estimated 5-year disease-free survival was 91.1% vs 87.5%.
At median follow-up of 63 months, estimated 5-year disease-free survival was 91.1% in the tamoxifen plus ovarian function suppression group vs 87.5% in the tamoxifen alone group (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.48–0.97, P = .033). Estimated 5-year overall survival was 99.4% vs 97.8% (HR = 0.31, 95% CI = 0.10–0.94; P = .029). In assessment of disease-free survival from time of randomization, with a median follow-up of 56 months, estimated 5-year disease-free survival was 89.8% vs 87.3% (HR = 0.69, 95% CI = 0.49–0.98; P = .036). In unplanned analyses, the hazard ratio for recurrence-free interval was 0.68 (95% CI = 0.47–0.999; P = .05) and the hazard ratio for breast cancer–free interval was 0.70 (95% CI = 0.49–1.01; P = .06).
The investigators concluded: “The addition of 2 years of ovarian function suppression to [tamoxifen] significantly improved [disease-free survival] compared with [tamoxifen] alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.”
Woo Chul Noh, MD, PhD, of the Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca and the Korea Institute of Radiological and Medical Sciences. For full disclosures of the study authors, visit jco.ascopubs.org.
