19P - Ribociclib + letrozole vs placebo + letrozole in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast c...

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Presenter Sunil Verma
Citation Annals of Oncology (2017) 28 (suppl_1): i7-i8. 10.1093/annonc/mdx137
Authors S. Verma1, M. Gil-Gil2, R. Hegg3, P. Wheatley-Price4, J. Kattan5, H. Bourgeois6, S. Sutradhar7, M. Miller7, M. Campone8
  • 1-, Tom Baker Cancer Centre, T2N 4N2 - Calgary, AB/CA
  • 2Institut Català D’oncologia, L’Hospitalet de Llobregat, 08908 - Barcelona/ES
  • 3Hospital Pérola Byington, Centro de Referência da Saúde da Mulher, 01317-000 - São Paulo/BR
  • 4-, University of Ottawa, ON K1N 6N5 - Ottawa/CA
  • 5-, Hôtel Dieu de France Hospital, 166830 - Beirut/LB
  • 6-, Centre Jean Bernard, 72000 - Le Mans/FR
  • 7-, Novartis Pharmaceuticals Corporation, NJ 07936 - East Hanover/US
  • 8-, Institut de Cancérologie de l’Ouest/René Gauducheau, 44 805 - Saint-Herblain/FR



Background: The presence of multiple metastases is prognostic of poor clinical outcomes in HR+, HER2– ABC. Increased disease symptoms arising from multiple metastatic sites may complicate clinical management and drug tolerability. In the MONALEESA-2 study, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + letrozole (LET) significantly improved progression-free survival (PFS) vs placebo (PBO) + LET in patients (pts) with HR+, HER2– ABC. Here we evaluate RIB + LET in pts with a high disease burden.

Methods: Postmenopausal women (N=668) with HR+, HER2– ABC and no prior systemic therapy for ABC were randomized 1:1 to RIB (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day, continuous) or PBO + LET. Inclusion criteria: measurable disease or ≥1 predominantly lytic bone lesion, and Eastern Cooperative Oncology Group performance status ≤1. Exclusion criteria: inflammatory breast cancer or central nervous system metastases. Pts with ≥3 metastatic sites were classed as having high disease burden. Endpoints: locally assessed PFS (primary), overall response rate, clinical benefit rate, and safety (all secondary).

Results: 441 pts had <3 metastatic sites (n, RIB vs PBO arm; 220 vs 221) and 227 pts ≥3 metastatic sites (114 vs 113). Median duration of RIB/PBO exposure (RIB vs PBO arm) was 12.1 vs 12.6 and 12.4 vs 11.7 months in pts with <3 and ≥3 metastatic sites, respectively. Treatment was discontinued in 40% vs 51% of pts with <3 metastatic sites (RIB vs PBO arm) and 45% vs 60% of pts with ≥3 metastatic sites; the most common reason for discontinuation was disease progression in 25% vs 40% and 29% vs 50% of pts, respectively. The most common, all-cause Grade 3/4 adverse events in the RIB + LET arm were neutropenia and reduced white blood cells in pts with <3 and ≥3 metastatic sites. RIB + LET increased PFS vs PBO + LET in pts with <3 metastatic sites (hazard ratio [HR]=0.607; 95% CI: 0.437–0.845; p=0.001) and in pts with ≥3 metastatic sites (HR=0.456; 95% CI: 0.298–0.700; p=0.0001).

Conclusion: RIB + LET significantly improved PFS compared with PBO + LET and had an acceptable safety profile in postmenopausal women with HR+, HER2– ABC and high disease burden.

Clinical trial identification


Legal entity responsible for the study

Novartis Pharmaceuticals Corporation


Novartis Pharmaceuticals Corporation


S. Verma: Advisory boards: Novartis, Roche, Pfizer, AstraZeneca, Eli Lilly, Amgen, BMS, Merck. P. Wheatley-Price: Advisory boards: Novartis (for lung cancer trials; not in relation to this abstract). S. Sutradhar: Employee of Novartis Pharmaceutical Corporation. M. Miller: Novartis employee and owns Novartis stocks. M. Campone: Grants: Novartis Advisory boards: Novartis, AstraZeneca, Pfizer, Roche Speaker bureau: Novartis. All other authors have declared no conflicts of interest.