%0 Journal Article
%A Hortobagyi, Gabriel N
%A Stemmer, Salomon M
%A Burris, Howard A
%A Yap, Yoon-Sim
%A Sonke, Gabe S
%A Paluch-Shimon, Shani
%A Campone, Mario
%A Blackwell, Kimberly L
%A André, Fabrice
%A Winer, Eric P
%A Janni, Wolfgang
%A Verma, Sunil
%A Conte, Pierfranco
%A Arteaga, Carlos L
%A Cameron, David A
%A Petrakova, Katarina
%A Hart, Lowell L
%A Villanueva, Cristian
%A Chan, Arlene
%A Jakobsen, Erik
%A Nusch, Arnd
%A Burdaeva, Olga
%A Grischke, Eva-Maria
%A Alba, Emilio
%A Wist, Erik
%A Marschner, Norbert
%A Favret, Anne M
%A Yardley, Denise
%A Bachelot, Thomas
%A Tseng, Ling-Ming
%A Blau, Sibel
%A Xuan, Fengjuan
%A Souami, Farida
%A Miller, Michelle
%A Germa, Caroline
%A Hirawat, Samit
%A O'Shaughnessy, Joyce
%T Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
%D 2016
%U http://hdl.handle.net/10668/10515
%X The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10-6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).
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