The addition of 2 years of ovarian function suppression (OFS) to tamoxifen (Nolvadex, Soltamox) yielded significantly improved disease-free survival (DFS) and overall survival compared with tamoxifen alone, according to the results of a study of premenopausal women with estrogen receptor-positive breast cancer published in the Journal of Clinical Oncology1.
“Although OFS in breast cancer has been studied for decades and has been used widely in clinical practice, evidence for the benefits of adding OFS to standard adjuvant TAM treatment is insufficient,” wrote study authors led by Hyun-Ah Kim, MD, PhD, of the Korea Cancer Center Hospital in Seoul.
Specifically, there is limited evidence regarding the optimal use of OFS for premenopausal women after they complete chemotherapy.
The new randomized, phase III trial included a total of 1,282 premenopausal women (aged 45 years or younger) with ER-positive breast cancer. All patients were treated with definitive surgery after completing chemotherapy. They were assessed every 6 months for 2 years after study enrollment for ovarian function based on follicular-stimulating hormone levels and vaginal bleeding history; if ovarian function was confirmed to be premenopausal at each such assessment, the patient was then randomized to either 5 years of tamoxifen alone (647 patients) or tamoxifen plus 2 years of OFS with goserelin (Zoladex) (635 patients).
Baseline characteristics were well balanced between the 2 groups. Most of both groups were aged 40-45 years, with fewer numbers aged 35-39 years and under 35. Slightly more than half the cohort had lymph-node positive disease, and just under 15% of each group had HER2-positive breast cancer (about one quarter of each group had unknown HER2 status).
After a median follow-up of 63 months, there were 132 DFS events in the intent-to-treat population; these included 28 locoregional recurrences, 84 distant metastases, 8 contralateral breast cancers, 11 other primary cancers, and 1 death without recurrence.
The 5-year DFS rate in the tamoxifen plus OFS group was 91.1%, compared with 87.5% with tamoxifen monotherapy, for a hazard ratio of 0.69 (95% CI, 0.48-0.97; P = 0.033).
Though the event rate for an overall survival analysis was “quite small,” there was still an advantage seen with the addition of OFS. The HR for OS was 0.31 (95% CI, 0.10-0.94; P = 0.029). This included 4 deaths in the OFS group and 14 deaths in the tamoxifen-only group.
“Ovarian function needs to be monitored longitudinally for at least two years in premenopausal patients who have been administered chemotherapy,” the authors concluded. “For those who remain in premenopausal state or resume ovarian function after chemotherapy, the addition of OFS for 2 years to standard tamoxifen treatment significantly improves DFS compared with tamoxifen alone.”
The results are consistent with previous trials including the SOFT trial, the final results of which were published in 2018.
In an editorial related to that trial, Marc E. Lippman, MD2, of the University of Miami Miller School of Medicine, wrote that the degree of side effects in that and the TEXT trial was higher with ovarian suppression than without, which has led many clinicians to offer OFS only to those patients at the highest risk. However, the benefits of ovarian suppression combined with either exemestane or tamoxifen were substantially the same in all categories of risk.
He added that available data “strongly favor” adding either a bisphosphonate or a RANKL inhibitor administered at 6-month intervals for 3 years to help prevent adverse events related to loss of bone density.
1.Kim, H., et. Al. (2019). Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial | Journal of Clinical Onc. Available at: https://ascopubs.org/doi/full/10.1200/JCO.19.00126.
2.Kim, H. (2019). Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial | Journal of Clinical Oncology. Available at: https://ascopubs.org/doi/full/10.1200/JCO.19.00126