Abstract P6-18-05: First-line ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled efficacy analysis
Authors: Tripathy D , Hortobagyi G , Chan A , Im S-A , Chia S , Yardley D , Esteva FJ , Hurvitz S , Kong O , Bao W , Rodriguez Lorenc K , Diaz-Padilla I , Slamon DJ 
Published: May 2019

Abstract
Background: In three separate Phase III randomized, placebo-controlled trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners prolonged progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the efficacy of RIB-based regimens of interest (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) in pts who were ET-naïve in the ABC setting, using pooled data from three Phase III trials: MONALEESA (ML)-2 (NCT01958021; all pts), ML-3 (NCT02422615; no prior ET for ABC subgroup only), and ML-7 (NCT02278120; RIB + NSAI subgroup only).
Methods: Postmenopausal pts with no prior ET for ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + either letrozole (2.5 mg/day) in ML-2 or FUL (500 mg every 28 days, with an additional dose on Day 15 of Cycle 1) in ML-3. In ML-7, premenopausal pts with no prior ET and ≤1 line of chemotherapy for ABC received RIB or PBO + goserelin (3.6 mg every 28 days) + NSAI (anastrozole [1 mg/day]/letrozole [2.5 mg/day]). The primary endpoint of all three trials was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DoR; ML-3 and -7). DoR was an exploratory endpoint in ML-2.
Results: Data were pooled for 820 pts treated with RIB + ET (ML-2: n=334; ML-3: n=238; ML-7: n=248) and 710 pts treated with PBO + ET (ML-2: n=334; ML-3: n=129; ML-7: n=247). As of the data cutoffs (ML-2: January 2, 2017; ML-3: November 3, 2017; ML-7: August 20, 2017), in the RIB + ET vs PBO + ET arms, 385 (47%) vs 234 (33%) pts remained on-treatment; the most common reason for discontinuation was disease progression (n=292 [36%] vs n=391 [55%]). In this pooled analysis, median PFS was prolonged for RIB + ET vs PBO + ET, with a hazard ratio of 0.570 (95% confidence interval [CI] 0.491–0.662); median PFS was 25.3 months (95% CI 23.9–29.6) vs 15.6 months (95% CI 14.4–16.9), respectively. Consistent PFS benefit for RIB + ET vs PBO + ET was observed across pt subgroups, including ECOG performance status, age, race, or presence/absence of liver and/or lung metastases or bone-only disease. Among all pts in the pooled analysis, the ORR was 41% for RIB + ET vs 28% for PBO + ET and the CBR was 79% vs 70%, respectively. In pts with measurable disease at baseline (RIB + ET: n=639; PBO + ET: n=542), the ORR was 51% for RIB + ET vs 37% for PBO + ET and the CBR was 79% vs 68%, respectively. In the RIB + ET vs PBO + ET arms, the median DoR was 26.7 months vs 20.0 months. A decrease in best percentage change from baseline in the sum of longest diameters per RECIST was observed in 86% of pts receiving RIB + ET vs 73% of pts receiving PBO + ET.
Conclusions: RIB in combination with various ET partners demonstrates improved clinical outcomes vs PBO + ET across a broad population of pts with HR+, HER2– ABC. These data provide further support for the use of RIB-based combinations in pre- and postmenopausal pts with HR+, HER2– ABC who have received no prior ET for advanced disease.
Citation Format: Tripathy D, Hortobagyi G, Chan A, Im S-A, Chia S, Yardley D, Esteva FJ, Hurvitz S, Kong O, Bao W, Rodriguez Lorenc K, Diaz-Padilla I, Slamon DJ. First-line ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled efficacy analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-05.