Author(s): Yen-Shen Lu, MD, PhD1; Eznal Izwadi Bin Mohd Mahidin, MD2; Hamdy Azim, MD3; Yesim Eralp, MD4; Yoon Sim Yap, MD, PhD5; Seock-Ah Im, MD, PhD6; Julie Rihani7; Erhan Gokmen, MD, PhD8; Ahmed El Bastawisy, MD9; Nuri Karadurmus, MD10; Yueh Ni Lim, MD11; Chun Sen Lim, MD12; K. Govind Babu, MD13; Konstantin Penkov, MD14; James Bowles, BMedSci15; Teresa Delgar Alfaro, Pharm D, MsC15; Jiwen Wu, PhD16; Melissa Gao, MD, PhD15; Khemaies Slimane, MD15; Nagi S. El Saghir, MD ns23@aub.edu.lb17; Le Thanh Duc, MD18; Wei-Pang Chung, MD19
PURPOSE
A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC).
PATIENTS AND METHODS
In this open-label, multi-center, randomized phase 2 trial, pre/perimenopausal women with clinically aggressive HR+/HER2− ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3-weeks-on, 1-week-off) plus letrozole/anastrozole and goserelin or investigator’s choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS).
RESULTS
Among 222 patients randomized to ribociclib plus ET (n=112) or combination CT (n=110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator’s judgment, and 31 (14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. Median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4-26.7 months) and 12.8 months (combination CT; 95% CI, 10.1-18.4 months); hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P=.003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (HR, 0.76; 95% CI, 0.55-1.06). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm
CONCLUSIONS
First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2− ABC.
Author Affiliations
1National Taiwan University Hospital, Taipei, Taiwan; 2Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 3School of Medicine, Cairo University, Cairo, Egypt; 4Acıbadem Research Institute of Senology, Acıbadem University, Istanbul, Turkey; 5National Cancer Centre Singapore, Singapore; 6Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; 7Independent Patient Advocate, Amman, Jordan; 8Ege University Faculty of Medicine, Izmir, Turkey; 9National Cancer Institute, Cairo University, Egypt; 10Gülhane Education and Research Hospital, University of Health Sciences, Ankara, Turkey; 11Sarawak General Hospital, Kuching, Sarawak, Malaysia; 12Hospital Sultan Ismail, Johor Bharu, Johor Darul Ta’zim, Malaysia; 13HCG Curie Centre of Oncology and Kidwai Memorial Institute of Oncology, Bangalore, India; 14Private Medical Institution Euromedservice, St Petersburg, Russian Federation; 15Novartis Pharma AG, Basel, Switzerland; 16Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 17American University of Beirut Medical Center, Beirut, Lebanon; 18National Cancer Hospital, Hanoi, Vietnam; 19National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;
