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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.

Author information

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

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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

PMID:
30589600
DOI:
10.1200/JCO.18.00296

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