Abstract P6-18-15: Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis
Authors: Burris HA , Chan A , Im S-A , Chia S , Tripathy D , Esteva FJ , Campone M , Bardia A , Kong O , Bao W , Diaz-Padilla I , Rodriguez Lorenc K , Yardley DA 
Published: May 2019

Abstract
Background: In Phase III trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners has demonstrated significantly prolonged progression-free survival vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the safety of RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) using pooled data from three Phase III trials (MONALEESA [ML]-2 [NCT01958021], -3 [NCT02422615], and -7 [NCT02278120]).
Methods: Postmenopausal pts with HR+, HER2– ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + letrozole (LET; 2.5 mg/day; ML-2 [no prior ET for ABC]) or FUL (500 mg, Days 1 and 15 of Cycle 1, then Day 1 of every cycle thereafter; ML-3; no or ≤1 prior line of ET for ABC]). Premenopausal pts (ML-7; no prior ET and ≤1 chemotherapy for ABC]) received RIB or PBO + anastrozole (1 mg/day)/LET (2.5 mg/day) + goserelin (3.6 mg every 28 days). Adverse events (AEs) were characterized per Common Terminology Criteria for Adverse Events v4.03; safety analyses included time to first event, duration of event, and rate of associated RIB/PBO discontinuations.
Results: Data for 1883 pts were pooled; 1065 pts received RIB + ET and 818 pts received PBO + ET (median exposure to study treatment: 17 and 13 months, respectively). Exposure-adjusted incidence rates for AEs of special interest were 561 and 131 per 100 pt-years in the RIB and PBO arms, respectively. The most common all-causality Grade 3/4 AEs (≥10% in any arm; RIB vs PBO) were neutropenia (59% vs 2%), leukopenia (18% vs 1%), and hypertension (13% vs 13%). A new Fridericia's corrected QT interval (QTcF) &gt;480 ms occurred in (n/N) 52/1054 (5%) vs 11/814 (1%) pts in the RIB vs PBO arms; a new QTcF &gt;500 ms occurred in 14/1054 (1%) vs 1/814 (&lt;1%) pts. Median time to first event for Grade ≥2 neutropenia, elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), and QTc prolongation in the RIB arm was 2, 12, and 2 weeks, respectively; median duration of first Grade ≥2 event was 4, 4, and 2 weeks. In the RIB arm vs PBO arms, 7% vs 3% of pts discontinued study treatment due to AEs; common all-grade AEs leading to RIB/PBO discontinuation (≥2% in any arm) were elevated ALT (4% vs &lt;1%) and elevated AST (2% vs 1%). Discontinuation due to QT prolongation occurred in 4 pts in the RIB arm and 2 in the PBO arm (both &lt;1%). All-grade serious AEs occurred in 25% of pts in the RIB arm vs 15% of pts in the PBO arm.
Conclusions: RIB in combination with various ET partners continues to demonstrate a predictable and manageable tolerability profile across a broad population of pts with HR+, HER2– ABC.
Citation Format: Burris HA, Chan A, Im S-A, Chia S, Tripathy D, Esteva FJ, Campone M, Bardia A, Kong O, Bao W, Diaz-Padilla I, Rodriguez Lorenc K, Yardley DA. Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety 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 P6-18-15.