2018 ASCO Annual Meeting!
Session: Breast Cancer—Metastatic
Type: Oral Abstract Session
Time: Sunday June 3, 8:00 AM to 11:00 AM
Location: Hall D2
Ribociclib (RIB) + fulvestrant (FUL) in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): Results from MONALEESA-3.
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 1000)
Author(s): Dennis J. Slamon, Patrick Neven, Stephen K. L. Chia, Seock-Ah Im, Peter A. Fasching, Michelino DeLaurentiis, Katarina Petrakova, Giulia Valeria Bianchi, Francisco J. Esteva, Miguel Martin, Xavier Pivot, Gena Vidam, Yingbo Wang, Cristina Karen Rodriguez Lorenc, Michelle Kristine Miller, Tanya Taran, Guy Heinrich Maria Jerusalem; UCLA Medical Center, Santa Monica, CA; Multidisciplinary Breast Centre, Universitair Ziekenhuis, Leuven, Belgium; BC Cancer Agency, Vancouver, BC, Canada; Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany; National Cancer Institute “Fondazione G. Pascale”, Napoli, Italy; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; NYU Langone Medical Center, New York, NY; Hospital General Universitario Gregorio Maranon, Madrid, Spain; CHRU de Besançon – IRFC, Besançon, France; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Novartis Pharma AG, Basel, Switzerland; CHU Liege and University of Liege, Liège, Belgium
Background: First-line RIB + letrozole significantly prolonged progression-free survival (PFS) in postmenopausal women with HR+, HER2– ABC. Here we report results from MONALEESA-3 (NCT02422615), a Phase 3 randomized, double-blind, placebo-controlled study of RIB + FUL in pts with HR+, HER2− ABC who received no or up to 1 line of prior endocrine therapy (ET) for ABC. Methods: Postmenopausal women with HR+, HER2– ABC were randomized 2:1 (stratified by presence of liver and/or lung metastases and prior ET) to RIB (600 mg/day; 3-weeks-on/1-week-off) + FUL (500 mg) or placebo (PBO) + FUL. Primary objective: investigator-assessed PFS. Secondary objectives included overall survival, overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 726 pts were enrolled. Baseline pt characteristics were balanced between arms. Median duration from randomization to data cut-off: 20.4 months. The primary objective was met: PFS was significantly improved in the RIB arm vs the PBO arm (hazard ratio: 0.593; 95% confidence interval [CI]: 0.480–0.732; p = 4.10×10–7); median PFS: 20.5 months; 95% CI: 18.5–23.5 vs 12.8 months; 95% CI: 10.9–16.3. Blinded independent review committee data supported primary efficacy results. Consistent PFS benefit was observed in pts with no (hazard ratio: 0.577; 95% CI: 0.415–0.802) and up to 1 line of prior ET for ABC (hazard ratio: 0.565; 95% CI: 0.428–0.744). In pts with measurable disease at baseline, ORR was 41% vs 29% (RIB vs PBO arm; p = 0.003); CBR was 69% vs 60% (p = 0.015). Common all-grade (G) adverse events (AEs; ≥30% of pts; RIB vs PBO arm) were neutropenia (70% vs 2%), nausea (45% vs 28%), and fatigue (31% vs 33%). In the RIB vs PBO arms, G3/4 neutropenia occurred in 47%/7% vs 0%/0% of pts, G3/4 increased ALT in 7%/2% vs < 1%/0%, and G3/4 increased AST in 5%/1% vs 1%/0%. Post-baseline QTcF > 480 ms (RIB vs PBO arm) occurred in 6% vs 3% of pts. Conclusions: RIB + FUL vs PBO + FUL significantly prolonged PFS and demonstrated a manageable safety profile in postmenopausal pts with HR+, HER2– ABC who received no or up to 1 line of prior ET for advanced disease. RIB + FUL may, therefore, be a treatment option for this pt population. Clinical trial information: NCT02422615