Abstract P6-18-04: Ribociclib with a non-steroidal aromatase inhibitor and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: MONALEESA-7 age subgroup analysis
Authors: Tripathy D , Campos-Gomez S , Lu Y-S , Franke F , Bardia A , Wheatley-Price P , Cruz FM , Hegg R , Cardoso F , Gaur A , Kong O , Diaz-Padilla I , Miller M , Hurvitz S 
Published: May 2019

Abstract
Background: Younger patients (pts) with breast cancer may experience more aggressive disease and are more likely to die from their cancer vs older pts. In the Phase III MONALEESA-7 study (NCT02278120), the addition of ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) to a non-steroidal aromatase inhibitor (NSAI) or tamoxifen (TAM) + goserelin significantly prolonged progression-free survival (PFS) in premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC; hazard ratio 0.553; p&lt;0.0001). RIB treatment benefit was observed irrespective of endocrine partner (NSAI or TAM). Here we report results from a MONALEESA-7 subgroup analysis in pts aged &lt;40 yrs and ≥40 yrs who received RIB or placebo (PBO) in combination with an NSAI + goserelin.
Methods: Pre- or perimenopausal women with HR+, HER2– ABC who had received no prior endocrine therapy and ≤1 line of chemotherapy for ABC were enrolled. Of the 672 pts randomized, 495 (74%) received RIB (600 mg/day, 3-weeks-on/1-week-off) or PBO + an NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) and goserelin (3.6 mg every 28 days). The primary endpoint was locally assessed PFS; secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety. A prespecified subgroup analysis was performed in pts aged &lt;40 yrs and ≥40 yrs.
Results: A total of 144 pts were aged &lt;40 yrs (RIB vs PBO arm: 78 vs 66) and 351 were aged ≥40 yrs (170 vs 181). As of August 20, 2017, in the RIB vs PBO arms, treatment was ongoing in 50% vs 23% of pts aged &lt;40 yrs and 54% vs 43% of pts aged ≥40 yrs; disease progression was the most common reason for treatment discontinuation (&lt;40 yrs: 37% vs 68%; ≥40 yrs: 35% vs 44%). Median PFS was prolonged in the RIB vs PBO arms both in pts aged &lt;40 yrs (not reached vs 10.8 months; hazard ratio 0.435; 95% confidence interval [CI] 0.276–0.686) and in pts aged ≥40 yrs (27.5 vs 19.1 months; hazard ratio 0.625; 95% CI 0.449–0.870). In pts with measurable disease, the ORR (RIB vs PBO arm) was 49% vs 32% in pts aged &lt;40 yrs and 51% vs 38% in pts aged ≥40 yrs; CBR was 81% vs 61% and 82% vs 65%, respectively. The most common Grade 3 adverse events (AEs; ≥5% of pts in either arm; RIB vs PBO arm) were neutropenia (&lt;40 yrs: 47% vs 5%; ≥40 yrs: 58% vs 3%), leukopenia (&lt;40 yrs: 18% vs 2%; ≥40 yrs: 14% vs 1%), diarrhea (&lt;40 yrs: 5% vs 0; ≥40 yrs: 1% vs 0), and increased alanine aminotransferase (&lt;40 yrs: 4% vs 2%; ≥40 yrs: 5% vs 1%); neutropenia was the only Grade 4 AE occurring in ≥5% of pts in either arm (&lt;40 yrs: 15% vs 0; ≥40 yrs: 8% vs 1%). New post-baseline QTcF &gt;480 ms (RIB vs PBO arm) occurred in 3% vs 2% of pts aged &lt;40 yrs and 7% vs 1% of pts aged ≥40 yrs.
Conclusions: Consistent treatment benefit was observed with RIB + NSAI vs PBO + NSAI in premenopausal women with HR+, HER2– ABC irrespective of age. RIB + NSAI had a manageable safety profile in pts aged &lt;40 yrs and in those aged ≥40 yrs, with a safety profile similar to that observed in the full study population.
Citation Format: Tripathy D, Campos-Gomez S, Lu Y-S, Franke F, Bardia A, Wheatley-Price P, Cruz FM, Hegg R, Cardoso F, Gaur A, Kong O, Diaz-Padilla I, Miller M, Hurvitz S. Ribociclib with a non-steroidal aromatase inhibitor and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: MONALEESA-7 age subgroup 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 P6-18-04.