Ribociclib as first-line therapy for HR-positive, advanced breast cancer

G. N. Hortobagyi, S. M. Stemmer, H. A. Burris, Y. S. Yap, G. S. Sonke, S. Paluch-Shimon, M. Campone, K. L. Blackwell, F. Andre, E. P. Winer, W. Janni, S. Verma, P. Conte, C. L. Arteaga, D. A. Cameron, K. Petrakova, L. L. Hart, C. Villanueva, A. Chan, E. JakobsenA. Nusch, O. Burdaeva, E. M. Grischke, E. Alba, E. Wist, N. Marschner, A. M. Favret, D. Yardley, T. Bachelot, L. M. Tseng, S. Blau, F. Xuan, F. Souami, M. Miller, C. Germa, S. Hirawat, J. O'Shaughnessy

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1309 Scopus citations


BACKGROUND 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). METHODS 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<1.29×10-5. RESULTS 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<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)1738-1748
Number of pages11
JournalNew England Journal of Medicine
Issue number18
StatePublished - Nov 3 2016

ASJC Scopus subject areas

  • General Medicine


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