Abstract P6-18-07: Ribociclib + endocrine therapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer presenting with visceral metastases: Subgroup analysis of phase III MONALEESA trials
Authors: Yardley DA , Chan A , Nusch A , Sonke GS , Yap Y-S , Bachelot T , Esteva FJ , Slamon DJ , Burris HA , Gaur A , Kong O , Diaz-Padilla I , Rodriguez Lorenc K , Wheatley-Price P 
Published: May 2019

Abstract
Background: Patients (pts) with advanced breast cancer (ABC) who present with visceral metastases (mets) have a poorer prognosis vs pts with non-visceral disease. In the Phase III MONALEESA (ML) trials, ribociclib (RIB) + endocrine therapy (ET) prolonged progression-free survival (PFS) vs placebo (PBO) + ET in hormone receptor-positive (HR+), HER2-negative (HER2–) ABC. Here we show data for pts with and without visceral mets from the ML-2, -3, and -7 trials.
Methods: Data were collated from 3 trials in HR+, HER2– ABC: in ML-2 (NCT01958021; data cutoff [DCO] Jan 2/4, 2017), postmenopausal pts (no prior ET for ABC) received RIB or PBO + letrozole; in ML-3 (NCT02422615; DCO Nov 3, 2017), postmenopausal pts (no prior ET for ABC subgroup only) received RIB or PBO + fulvestrant; in ML-7 (NCT02278120; DCO Aug 20, 2017), premenopausal pts (no prior ET and ≤1 chemotherapy for ABC) received RIB or PBO + goserelin + anastrozole/letrozole. Endpoints; primary: local PFS; secondary: overall response rate (ORR), clinical benefit rate (CBR), safety.
Results: Of all 820 pts treated with RIB + ET, 484 (59%) had visceral mets (ML-2 197/334; ML-3 137/238; ML-7 150/248); of all 710 pts treated with PBO + ET, 416 (59%) had visceral mets (ML-2 196/334; ML-3 77/129; ML-7 143/247). Median PFS was prolonged for RIB vs PBO in pts with and without visceral mets (Table). ORR and CBR were also higher for RIB vs PBO in pts with and without visceral mets. The most common (≥10% of pts in any arm) Grade [G] 3 and 4 adverse events (AEs) for each trial are shown in the table; no G4 AEs occurred in ≥10% of pts in ML-3.
Visceral metsNo visceral metsML-2 Median PFS (RIB/PBO), months (95% CI)24.9 (22.2–30.9)/13.4 (12.7–16.5)25.3 (22.2–NR)/18.2 (15.0–24.6)Hazard ratio (95% CI)0.538 (0.408–0.709)0.634 (0.448–0.897) ORR (RIB/PBO),* %48/3735/17 CBR (RIB/PBO),† %79/7282/75 Most common (≥10% in any arm) G3 AEs (RIB/PBO), %Neutropenia56/147/1Leukopenia19/121/&lt;1Hypertension11/1115/15 Most common (≥10% in any arm) G4 AEs (RIB/PBO), %Neutropenia10/09/0 ML-3 Median PFS (RIB/PBO), months (95% CI)NR (19.1–NR)/16.5 (9.0–NR)NR (NR–NR)/21.9 (14.8–NR)Hazard ratio (95% CI)0.610 (0.403–0.926)0.521 (0.295–0.921) ORR (RIB/PBO),* %46/2931/21 CBR (RIB/PBO),† %74/6075/81 Most common (≥10% in any arm) G3 AEs (RIB/PBO), %Neutropenia50/045/0Leukopenia12/010/0Increased ALT6/012/0 ML-7 Median PFS (RIB/PBO), months (95% CI)23.8 (14.8–NR)/10.4 (7.2–12.9)27.5 (NR–NR)/19.3 (16.5–NR)Hazard ratio (95% CI)0.507 (0.367–0.700)0.609 (0.377–0.984) ORR (RIB/PBO),* %45/3630/19 CBR (RIB/PBO),† %79/5783/81 Most common (≥10% in any arm) G3 AEs (RIB/PBO), %Neutropenia54/356/4Leukopenia14/116/1 Most common (≥10% in any arm) G4 AEs (RIB/PBO), %Neutropenia11/&lt;19/0CI, confidence interval; NR, not reached. *ORR = complete response + partial response; †CBR = complete response + partial response + (stable disease + non-complete response/non-progressive disease ≥24 weeks).
Conclusions: Although the presence of visceral mets is associated with a poorer prognosis, RIB + ET is an effective and well-tolerated treatment option for pts with HR+, HER2– ABC irrespective of the presence of visceral mets.
Citation Format: Yardley DA, Chan A, Nusch A, Sonke GS, Yap Y-S, Bachelot T, Esteva FJ, Slamon DJ, Burris HA, Gaur A, Kong O, Diaz-Padilla I, Rodriguez Lorenc K, Wheatley-Price P. Ribociclib + endocrine therapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer presenting with visceral metastases: Subgroup analysis of phase III MONALEESA 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 P6-18-07.