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Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
Gabriel N Hortobagyi1, Salomon M Stemmer1, Howard A Burris1
1From the University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.), and Texas Oncology-Baylor Charles A. Sammons Cancer Center and the U.S. Oncology Network, Dallas (J.O.) - all in Texas; Davidoff Center, Rabin Medical Center, Tel Aviv University, Tel Aviv (S.M.S.), and Sheba Medical Center, Ramat Gan (S.P.-S.) - both in Israel; the Sarah Cannon Research Institute (H.A.B., D.Y.), Vanderbilt-Ingram Cancer Center (C.L.A.), and Tennessee Oncology (D.Y.) - all in Nashville; National Cancer Center Singapore, Singapore (Y.-S.Y.); Netherlands Cancer Institute and BOOG Study Center, Amsterdam (G.S.S.); Institut de Cancérologie de l'Ouest/René Gauducheau, Saint-Herblain (M.C.), Institut Gustave Roussy, Université Paris Sud, Villejuif (F.A.), University Hospital of Besançon, Besançon (C.V.), and Centre Léon Bérard, Lyon (T.B.) - all in France; Duke University Medical Center, Durham, NC (K.L.B.); Dana-Farber Cancer Institute, Boston (E.P.W.); University of Ulm, Ulm (W.J.), Onkologische Praxis, Velbert (A.N.), University of Tübingen, Tübingen (E.-M.G.), and Joint Practice for Interdisciplinary Oncology and Hematology, Freiburg (N.M.) - all in Germany; Tom Baker Cancer Centre, Calgary, AB, Canada (S.V.); University of Padua and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy (P.C.); Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh (D.A.C.); Masaryk Memorial Cancer Institute, Brno, Czech Republic (K.P.); Florida Cancer Specialists-Sarah Cannon Research Institute, Fort Myers (L.L.H.); Breast Cancer Research Centre-Western Australia and Curtin University, Perth, Australia (A.C.); Department of Oncology, Vejle Hospital, Vejle, Denmark (E.J.); Arkhangelsk Clinical Oncology Dispensary, Arkhangelsk, Russia (O.B.); Hospital Universitario Virgen de la Victoria, Institute of Biomedical Research in Málaga, Málaga, Spain (E.A.); Oslo University Hospital, Oslo (E.W.); Virginia Cancer Specialists, Arlington (A.M.F.); Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan (L.-M.T.); Rainier Hematology-Oncology, Northwest Medical Specialties, Puyallup, WA (S.B.); Novartis Pharmaceuticals, East Hanover, NJ (F.X., M.M., C.G., S.H.); and Novartis Pharma, Basel, Switzerland (F.S.).
The addition of ribociclib to letrozole significantly improved progression-free survival for postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer. This combination therapy offers a new first-line treatment option, though it is associated with increased myelosuppression.
Area of Science:
- Oncology
- Pharmacology
Background:
- Hormone receptor-positive (HR+), HER2-negative advanced breast cancer often develops resistance to endocrine therapy.
- Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors show potential in overcoming or delaying this resistance.
Purpose of the Study:
- To evaluate the efficacy and safety of ribociclib, a selective CDK4/6 inhibitor, combined with letrozole as a first-line treatment for advanced HR+, HER2-negative breast cancer.
- To compare progression-free survival (PFS) and overall survival (OS) between patients receiving ribociclib plus letrozole and those receiving placebo plus letrozole.
Main Methods:
- A randomized, placebo-controlled, phase 3 trial involving 668 postmenopausal women with previously untreated HR+, HER2-negative advanced breast cancer.
- Patients were assigned to receive either ribociclib (600 mg/day, 3 weeks on/1 week off) plus letrozole (2.5 mg/day) or placebo plus letrozole.
- The primary endpoint was investigator-assessed progression-free survival; secondary endpoints included overall survival and safety.
Main Results:
- Ribociclib plus letrozole significantly prolonged progression-free survival compared to placebo plus letrozole (hazard ratio, 0.56; P=3.29×10-6).
- At 18 months, the PFS rate was 63.0% with ribociclib versus 42.2% with placebo.
- The overall response rate was higher in the ribociclib group (52.7% vs. 37.1%). Common grade 3/4 adverse events included neutropenia and leukopenia, with higher rates in the ribociclib arm.
Conclusions:
- First-line treatment with ribociclib plus letrozole significantly improves progression-free survival in patients with HR+, HER2-negative advanced breast cancer.
- The combination therapy is a viable option, but requires monitoring for myelosuppression.
- This study supports CDK4/6 inhibition as a strategy to enhance endocrine therapy efficacy in advanced breast cancer.
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