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 Anticancer Agents
Breast Cancer
Biological Therapy
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.