Abstract P1-10-06: A randomized phase II trial evaluating the endocrine activity and efficacy of neoadjuvant degarelix versus triptorelin in premenopausal patients receiving letrozole for primary endocrine responsive breast cancer (TREND; IBCSG 41-13)
Authors: Colleoni M , Gray K , Munzone E , Dellapasqua S , Zamagni C , Gianni L , Johansson H , Viale G , Kammler R , Maibach R , Rabaglio-Poretti M , Di Leo A , Coates AS , Gelber RD , Regan MM , Goldhirsch A 
Published: February 2018

Background: Neoadjuvant endocrine therapy (NET) with gonadotropin-releasing hormone (GnRH) agonist and aromatase inhibitors is effective in selected premenopausal patients (pts). Degarelix, an antagonist of GnRH, has immediate onset of action through binding to GnRH receptors in the pituitary gland and thereby suppressing the production of LH and FSH. Its suppressing activity in premenopausal women might be faster and free of estrodial breakthrough on continued treatment compared with a GnRH angonist, and thereby provide significant clinical value for pts who are candidates for short-term NET.

Methods: Eligible pts were premenopausal women with cT2-4b, any nodal stage, ER and PgR &gt;50%, HER2-negative (by IHC and/or ISH) breast cancer who were not candidates for breast conserving surgery. Premenopausal status was determined locally with estradiol (E2) levels &gt;54 pg/mL (or &gt;198 pmol/L), measured within 14 days prior to randomization. Pts were randomized 1:1 to Triptorelin (T) 3.75 mg i.m. on day 1 of every cycle or Degarelix (D) 240 mg s.c. given as two injections of 120 mg on day 1 of cycle 1, then 80 mg s.c. on day 1 of cycles 2-6 with letrozole (L) 2.5 mg/day for 6 cycles. Each cycle was 28 days. Definitive surgery was performed within 2-3 weeks after the last administration of T or D. Serum was collected prior to the first injection (baseline), 24 and 72 hours, 7 and 14 days, then prior to injection on day 1 of cycles 2-6. The primary endpoint was time to optimal ovarian function suppression (OFS) calculated as time from the first injection of D or T to the first assessment of centrally assessed 17-β-estradiol (E2) level in the range of optimal OFS (≤2.72 pg/mL or ≤10 pmol/L) during the 6 cycles of NET. The trial had 90% power to detect a difference using a logrank test, 2-sided α=0.05. Secondary endpoints included tolerability, Ki67changes, PEPI score, best overall response. NCT02005887

Results: TREND completed accrual of 51 pts in January 2017. A preliminary analysis based on the first 45 pts is reported here. 89% of patients were ≥40 yrs, 76% had T1-2 and 22% T3 tumors, and 51% were node-positive. Dominant histology type was ductal (93%). The table summarizes centrally-assessed E2 according to treatment at baseline and for the first 5 assessment time points indicating immediate suppression for the D+L arm. E2 levels on day 1 of cycles 2-6 were all below the limit of quantification (0.625 pg/mL) for the D+L arm. For the T+L arm continued OFS was not maintained in 4 pts.

 BaselineCycle 1Cycle 2Day:01371429No. Pts      D+L222221212221T+L232321232222Median (IQR)     D+L96.2 (64.2,206.8)10.1 (4.0,21.8)0.6 (0.6,1.0)0.6 (0.6,0.6)0.6 (0.6,0.6)0.6 (0.6, 0.6)T+L85.1 (49.7,118.0)37.4 (17.9,59.2)12.8 (7.7,23.8)9.0 (1.2,29.7)0.6 (0.6,1.4)0.6 (0.6, 0.6)

Conclusion: Evidence from this first analysis demonstrates rapid and maintained OFS with the combination of D+L as a NET in premenopausal breast cancer patients. The final analysis of the total population, including secondary endpoints, will be presented at the symposium.

Citation Format: Colleoni M, Gray K, Munzone E, Dellapasqua S, Zamagni C, Gianni L, Johansson H, Viale G, Kammler R, Maibach R, Rabaglio-Poretti M, Di Leo A, Coates AS, Gelber RD, Regan MM, Goldhirsch A. A randomized phase II trial evaluating the endocrine activity and efficacy of neoadjuvant degarelix versus triptorelin in premenopausal patients receiving letrozole for primary endocrine responsive breast cancer (TREND; IBCSG 41-13) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-06.