Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Yen‐Shen Lu, Eznal Izwadi Bin Mohd Mahidin, Hamdy A. Azim, Yeşim Eralp, Yoon Sim Yap, Seock‐Ah Im, Julie Rihani, Erhan Gökmen, Ahmed El Bastawisy, Nuri Karadurmuş, Yueh Ni Lim, Chun Sen Lim, Le Thanh Duc, Wei‐Pang Chung, Govind Babu, Konstantin Penkov, James Bowles, T. Delgar Alfaro, Jiwen Wu, Melissa Gao, Khémaies Slimane, Nagi S. El Saghir, Adher Alsayed, Ahmed El Bastawisy, Ajay Gogia, Chaiyut Charoentum, Chanchal Goswami, Chien-Ting Liu, Chun Sen Lim, Е. В. Артамонова, Erhan Gökmen, Esat Namal, Eznal Izwadi Mohd Mahidin, Fadi Farhat, Flora Chong Li Tze, Gül Başaran, Hakan Harputluoğlu, Hamdy A. Azim, Hikmat Abdel‐Razeq, Hesham Ahmed ElGhazaly, K. Govind Babu, Konstantin Penkov, Le Thanh Duc, Ling‐Ming Tseng, Liudmila Osmanova, Ludmila Zhukova, Meher Lakshmi Konatum, Mehmet Alı Nahıt Şendur, Ming‐Shen Dai, Mona Ayoubi, Nagi S. El Saghir, Naiyarat Prasongsook, Napa Parinyanitikul, Nikita Volkov, Nuri Karadurmuş, Patrapim Sunpaweravong, Peter Ang, Pei Jye Voon, Rabab Gaafar, Rasha Abdel Motagaly, Richard Khanyile, Sema Sezgin Göksu, Shin‐Cheh Chen, Sudeep Gupta, Su Mien Lynette Ngo, Swee Hsia Choong, Terence Aik Huang Tan, Umut Demırcı, Wei‐Pang Chung, Wen‐Son Hsieh, Yen‐Shen Lu, Yeşim Eralp, Yoon Sim Yap, Yuan‐Ching Chang, Yueh Ni Lim
Abstract
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). METHODS In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2– ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once 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 end point was progression-free survival (PFS). RESULTS Among 222 patients randomly assigned 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 nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The 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 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 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 (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSION 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.