Abstract P6-18-14: Patient-reported outcomes with ribociclib-based therapy in hormone receptor-positive, HER2-negative advanced breast cancer: results from the phase III MONALEESA-2, -3, and -7 trials
Authors: Beck JT , Neven P , Esteva FJ , Bardia A , Harbeck N , Hurvitz S , O'Shaughnessy J , Verma S , Lanoue B , Alam J , Kong O , Chandiwana D , Chia S 
Published: May 2019

Abstract
Background: In the Phase III MONALEESA (ML) trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + endocrine therapy (ET) significantly improved 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 report key patient-reported outcomes (PROs) for pts treated with RIB-based regimens of interest (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) in the ML-2, -3, and -7 trials.
Methods: Postmenopausal pts with HR+, HER2– ABC and no prior ET for advanced disease received RIB (600 mg/day; 3-weeks-on/1-week-off) + letrozole (2.5 mg/day; ML-2 [NCT01958021]), or FUL (500 mg every 28 days, with an additional dose on Day 15 of Cycle [C] 1; ML-3 [no prior ET for ABC subgroup only; NCT02422615]). Premenopausal pts with no prior ET and ≤1 line of chemotherapy for advanced disease received RIB + NSAI (anastrozole [1 mg/day]/letrozole [2.5 mg/day]) + goserelin (3.6 mg every 28 days; ML-7 [NCT02278120]). The primary endpoint for all trials was PFS. PROs were a secondary endpoint of all trials and were evaluated using EORTC QLQ-C30, QLQ-BR23 (ML-2 and ML-7), EQ-5D-5L, WPAI-GH (ML-7 only), and BPI-SF (ML-3 only) questionnaires. Changes from baseline and time to 10% deterioration (TTD) in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively.
Results: A total of 1530 pts were included in this analysis. Questionnaire compliance was high across trials (ML-2/ML-3: &gt;90%; ML-7: &gt;80%). On-treatment HRQoL (EORTC QLQ-C30 global health status/quality of life [QoL] score) was maintained from baseline up to C34, C28, and C17 in both treatment arms for ML-2, ML-3, and ML-7, respectively. In ML-7, mean overall HRQoL scores continued to improve in the RIB arm from C18 to C28, but scores decreased in the PBO arm. At end of treatment, mean overall HRQoL scores decreased in both arms across trials. Median TTD (RIB vs PBO) was similar between arms, favoring the RIB arms (ML-2: 27.7 vs 27.6 months; hazard ratio 0.944; 95% confidence interval [CI] 0.720–1.237; ML-3: not reached [NR] vs 22.4 months; hazard ratio 0.721; 95% CI 0.484–1.074; ML-7: 24.0 vs 19.4 months; hazard ratio 0.759; 95% CI 0.561–1.028). Clinically meaningful reductions in EORTC QLQ-C30 pain score (&gt;5 points from baseline) were observed in the RIB arm of ML-2 from as early as C3 and were sustained vs only at C7 and C13 in the PBO arm. Clinically meaningful reductions in pain were observed from C22 to C28 in the RIB arm of ML-7 vs only at C28 in the PBO arm. In ML-3, clinically meaningful reductions in pain were observed from C3 to C5, C11–17, and at C22 and C28 in the RIB arm vs C17–C25 in the PBO arm. Furthermore, median TTD of the BPI-SF pain severity index score was NR in either arm of ML-3 (hazard ratio 0.858; 95% CI 0.554–1.330).
Conclusions: In addition to significantly prolonging PFS, RIB consistently maintains QoL regardless of ET combination partner. RIB + ET is also associated with clinically meaningful reductions in pain vs PBO + ET across a broad population of pts with HR+, HER2– ABC.
Citation Format: Beck JT, Neven P, Esteva FJ, Bardia A, Harbeck N, Hurvitz S, O'Shaughnessy J, Verma S, Lanoue B, Alam J, Kong O, Chandiwana D, Chia S. Patient-reported outcomes with ribociclib-based therapy in hormone receptor-positive, HER2-negative advanced breast cancer: results from the phase III 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 P6-18-14.