Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer

Author(s): Gabriel N. Hortobagyi, M.D., Salomon M. Stemmer, M.D., Howard A. Burris, M.D., Yoon-Sim Yap, M.D., Gabe S. Sonke, M.D., Ph.D., Lowell Hart, M.D., Mario Campone, M.D., Ph.D., Katarina Petrakova, M.D., Ph.D., Eric P. Winer, M.D., Wolfgang Janni, M.D., Ph.D., Pierfranco Conte, M.D., Ph.D., David A. Cameron, M.D., et al.
Source: N Engl J Med 2022; 386:942-950 DOI: 10.1056/NEJMoa2114663
Lucio Gordan MD

Dr. Lucio Gordan's Thoughts

Another landmark study supporting the use CDK4/6 drugs along with endocrine therapy in the breast cancer metastatic setting. Missed opportunities insofar as adding CDK 4/6 drugs to endocrine blockade are a concern, since the OS survival difference is significant.


In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.


Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan–Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.


After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P=0.008). No new safety signals were observed.


First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo.

Author Affiliations

From the Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.), and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center (C.L.A.), and Baylor University Medical Center, Texas Oncology, US Oncology (J.O.), Dallas — all in Texas; the Institute of Oncology, Davidoff Center, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel (S.M.S.); Sarah Cannon Research Institute, Nashville (H.A.B.); the Department of Medical Oncology, National Cancer Centre Singapore, Singapore (Y.-S.Y.); the Department of Medical Oncology, Netherlands Cancer Institute and Borstkanker Onderzoek Groep Study Center, Amsterdam (G.S.S.); Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers (L.H.); the Department of Medical Oncology, Institut de Cancérologie de l’Ouest–René Gauducheau, Saint-Herblain (M.C.), and the Department of Medical Oncology, Institut Gustave Roussy, Medical School, Université Paris-Saclay, Villejuif (F.A.) — both in France; the Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic (K.P.); the Department of Medical Oncology, Dana–Farber Cancer Institute, Boston (E.P.W.); the Department of Gynecology, University of Ulm, Ulm, Germany (W.J.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and the Division of Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua, Italy (P.C.); the Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh (D.A.C.); Novartis Pharmaceuticals, East Hanover, NJ (J.P.Z., A.C.); and Novartis Pharma, Basel, Switzerland (T.T., F.L.G., P.S.).

1 thought on “Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer”

  1. Hi I will present further data from this trial in a Poster discussion session at ASCO in June. It will be overall survival data on patients who needed dose reductions with Ribociclib in the trial. it seems to me the drug should be considered more first line given the very strong survival data which is among the best ever seen in MBC

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