Abstract 39P
Background
In the phase III MONALEESA-7 (ML-7) trial, ribociclib (RIB)+endocrine therapy (ET; goserelin and either a nonsteroidal aromatase inhibitor [AI] or tamoxifen) showed significant survival benefit in premenopausal patients with hormone receptor–positive (HR+), HER2− negative (HER2−) advanced breast cancer (ABC). Of note, goserelin has been used with AI or tamoxifen to enhance the estrogen signaling inhibition in premenopausal patients. We aimed to evaluate estradiol (E2) suppression in premenopausal patients treated with RIB+ET in ML-7 trial. E2 suppression is important to lower disease progression and serve as a common treatment strategy for HR+ ABC.
Methods
From the main analysis set (N=672), premenopausal patients with HR+/HER2− ABC treated with RIB or placebo+ET were included to evaluate the E2 level at Cycle 1 Day 1 (C1D1) and Cycle 3 Day 15 (C3D15); we set the criteria E2 ≤2.7 pg/mL at C3D15 as E2 suppression.
Results
In this post hoc analysis, a total of 163 patients were evaluated for the E2 level both at C1D1 and C3D15. A total of 85 patients on RIB treatment group had 100% E2 suppression (E2 ≤2.7 pg/mL) after treatment initiation and 78 patients on placebo had 93.1% E2 suppression (Table). The E2 levels decreased between treatment cycles C1D1 and C3D15 and was higher in the RIB group vs placebo. Among patients with E2 >2.7 pg/mL at C3D15 or vaginal hemorrhage during treatment phase, there was a significant decrease in the E2 levels between treatment cycle C1D1 and C3D15 in RIB group (mean [SD] change: −131.57 [136.39] P=0.031) Table: 39P
E2 suppression and E2 levels in patients with HR+, HER2− ABC
| Parameter | Overall N=163 | RIB group n=85 | Placebo n=78 | P value* |
| E2 suppression, n (%) | ||||
| Yes (E2 ≤ 2.7pg/mL at C3D15) | 85 (100.0) | 73 (93.6) | 0.0234 | |
| No (E2 > 2.7pg/mL at C3D15) | 5 (3.1) | 0 (0) | 5 (6.4) | |
| Patients with E2 >2.7 pg/mL at C3D15 or vaginal hemorrhage during treatment phase | Overall N=14 | RIB group n=6 | Placebo n=8 | P value † |
| C1D1 | ||||
| E2 level, mean (SD) | 102.93 (95.08) | 132.25 (136.23) | 80.94 (47.36) | 0.490 |
| C3D15 | ||||
| E2 level, mean (SD) | 5.29 (9.51) | 0.68 (0.67) | 8.75 (11.65) | 0.137 |
*E2 levels by Fisher exact test†P-value by Mann-Whitney U-test
.Conclusions
The findings suggest that addition of RIB to ET and goserelin could further enhance E2 suppression in premenopausal patients with HR+/HER2− ABC. Given the nature of analyses and the observed variations in E2 levels, these results should be cautiously interpreted warranting future studies.
Clinical trial identification
NCT02278120.
Editorial acknowledgement
The authors thank Renuka Reddy and Lakshmi Kasthurirangan of Novartis Healthcare Pvt Ltd (Hyderabad, India) for providing medical writing support in the preparation of this abstract.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
All authors have declared no conflicts of interest.