Abstract P6-18-06: Ribociclib treatment benefit in patients with advanced breast cancer with ≥1 dose reduction: Data from the MONALEESA-2, -3, and -7 trials
Authors: Beck JT , Neven P , Sohn J , Chan A , Sonke GS , Bachelot T , Campos-Gomez S , Martin M , Bardia A , Alam J , Miller M , Diaz-Padilla I , Kong O , Hart L 
Published: May 2019

Abstract
Background: In the MONALEESA (ML) trials, addition of ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) to endocrine therapy (ET) prolonged progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). RIB was generally well tolerated, with adverse events (AEs) managed effectively by dose modifications. Here we present efficacy data for RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) from ML-2, -3, and -7 in pts who received no prior ET for ABC and who had ≥1 RIB dose reduction, to explore the efficacy of RIB in pts who need to dose reduce.
Methods: Pts included in this analysis were: postmenopausal women with HR+, HER2– ABC and no prior ET for ABC who received RIB (600 mg; 3-weeks-on/1-week-off) with letrozole (2.5 mg/day; ML-2 [NCT01958021]), or FUL (500 mg per label; ML-3 [NCT02422615]); and premenopausal women with no prior ET and ≤1 line of chemotherapy for ABC who received RIB with an NSAI (anastrozole: 1 mg/day; letrozole: 2.5 mg/day; ML-7 [NCT02278120]) plus goserelin (3.6 mg every 28 days). Dose reductions for RIB (600 to 400 to 200 mg) were permitted. Primary endpoint was PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety.
Results: In ML-2, -3, and -7, ≥1 RIB dose reduction occurred (n/N) in 169/334 (51%), 92/238 (39%), and 91/246 (37%) pts assigned to RIB, respectively. AEs were the main reason for dose reduction, with all-grade neutropenia the most common AE leading to dose reduction (ML-2 69%, ML-3 80%, ML-7 82%). Median PFS (months) was prolonged with RIB vs placebo in pts without a RIB dose reduction (ML-2: 27.7 vs 16.0; ML-3: not reached [NR] vs 18.3; ML-7: 23.8 vs 13.8); median PFS in pts with ≥1 RIB dose reduction was: ML-2 25.3, ML-3 NR, and ML-7 27.5 months. In pts with measurable disease and without a RIB dose reduction, ORR was 46% (ML-2), 43% (ML-3), and 48% (ML-7); CBR was 70%, 68%, and 79%, respectively. In pts with measurable disease and ≥1 RIB dose reduction, ORR was 62% (ML-2), 57% (ML-3), and 55% (ML-7); CBR was 88%, 85%, and 88%, respectively. The most common Grade 3/4 AEs in the RIB vs placebo groups (≥5% of pts in either ML trial, irrespective of causality or dose reduction) were neutropenia (ML-2: 62% vs 1%; ML-3: 55% vs 0; ML-7: 65% vs 4%), leukopenia (ML-2: 21% vs 1%; ML-3: 12% vs 0; ML-7: 16% vs 1%), hypertension (ML-2: 13% vs 13%; ML-3: 5% vs 5%; ML-7: 2% vs 3%), increased alanine aminotransferase (ML-2: 10% vs 1%; ML-3: 10% vs 0; ML-7: 5% vs 1%), and increased aspartate aminotransferase (ML-2: 6% vs 1%; ML-3: 6% vs 0; ML-7: 4% vs 1%).
Conclusions: Results from the ML-2, -3, and -7 trials suggest that pts who start on 600 mg of RIB and require dose reduction for the management of their AEs, or for other reasons, continue to derive clinical benefit.
Citation Format: Beck JT, Neven P, Sohn J, Chan A, Sonke GS, Bachelot T, Campos-Gomez S, Martin M, Bardia A, Alam J, Miller M, Diaz-Padilla I, Kong O, Hart L. Ribociclib treatment benefit in patients with advanced breast cancer with ≥1 dose reduction: Data from the MONALEESA-2, -3, and -7 trials [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 P6-18-06.