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J Clin Oncol. 2019 Feb 10;37(5):386-395. doi: 10.1200/JCO.18.00296. Epub 2018 Dec 27.

Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial.

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1 IEO, European Institute of Oncology Istituto di Recovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
2 Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA.
3 S Orsola Hospital, Bologna, Italy.
4 Ospedale Infermi di Rimini, Azienda Unita Sanitaria (AUSL) della Romagna, Italy.
5 International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
6 Hospital of Prato-AUSL Toscana Centro, Prato, Italy.
7 International Breast Cancer Study Group and University of Sydney, Sydney, Australia.
8 Frontier Science and Technology Research Foundation and Harvard Medical School, Boston, MA.
9 International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.



To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer.


Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2-negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level ≤ 2.72 pg/mL [≤ 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided α of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms.


Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P < .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and triptorelin plus letrozole were as expected.


In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.

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