#VisualAbstract: Neoadjuvant degarelix versus triptorelin in premenopausal patients who receive letrozole for locally advanced endocrine-responsive breast cancer: a randomized phase II trial

Ovarian function suppression (OFS) is considered an important aspect of treatment in premenopausal women with advanced endocrine-responsive breast cancer. Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist, which, when bound to GnRH receptors in the pituitary, results in a decreased secretion of gonadotropins. In men, this leads to a rapid decrease in the production of testosterone, and degarelix is approved in the treatment of prostate cancer. In premenopausal women, OFS may be achieved faster with degarelix than with GnRH analogs. The aim of this study was to compare the endocrine activity of triptorelin versus degarelix in premenopausal patients with breast cancer receiving letrozole as neoadjuvant endocrine therapy (NET). In this randomized controlled trial, 51 premenopausal women with stage cT2 to 4b, estrogen receptor and progesterone receptor greater than 50%, and human epidermal growth factor receptor 2-negative invasive breast cancer were randomized to receive triptorelin 3.75 mg (administered intramuscularly on day 1 of every cycle) or degarelix 240 mg (administered subcutaneously on day 1 of cycle 1, and then 80 mg on day 1 of cycles 2-6), both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2-3 weeks after the last injections. Researchers found that the time to optimal OFS was significantly shorter in patients that received degarelix and letrozole, when compared to the control group (median 3 vs. 14 days, HR 3.05, 95% CI 1.65 to 5.65, p<0.001). OFS was also maintained during subsequent cycles for all patients that received degarelix and letrozole. Conversely, 15.4% of patients in the control group had suboptimal OFS after the first cycle. This study therefore shows that in premenopausal women receiving letrozole for NET, OFS is achieved more quickly and sustained more effectively with the use of degarelix as compared to triptorelin.

Click to read the study in JCO

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