CDK4/6 inhibition in early and metastatic breast cancer: A review |
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| Affiliation: | 1. Institute of Cancer Policy, King''s College London, UK;2. University of Manitoba and CancerCare Manitoba, Canada;1. University of Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724, USA;2. Department of Medicine, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA;3. Department of Pathology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA;1. Istituto Europeo di Oncologia, via Ripamonti 435, 20141, Milan, Italy;2. Servicio Oncologia Médica, Vall d''Hebron University Hospital, Vall d''Hebron 119–129, 08035, Barcelona, Spain;3. The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX, 77030, USA;4. Istituto Oncologico Veneto, Via Gattamelata 64, 35128, Padua, Italy;5. University of Padova, Via Giustiniani 22, 35121, Padua, Italy;6. University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands;7. Erasmus Medical Center Cancer Institute, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands;8. Highlands Oncology Group, 3232 N North Hills Blvd, Fayetteville, AR, 72703, USA;9. Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA;10. Oncología Médica, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain;11. Centre Jean Perrin, Unicancer and EA 4677 Université d''Auvergne, 58 rue Montalembert, 63011, Clermont-Ferrand, France;12. Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA;13. Novartis Institutes for BioMedical Research, 230 Massachusetts Avenue, Cambridge, MA, 02139, USA;14. University of California, Los Angeles, 2825 Santa Monica Blvd, Suite 211, Santa Monica, CA, 90404, USA;1. Division of Hematology Oncology, Department of Medicine, Columbia University Medical Center, New York, NY;2. James J. Peters VAMC, Bronx, NY;1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;2. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;3. Department of Pathology, Harvard Medical School, Boston, MA 02115, USA;4. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA 02215, USA;5. Center for Functional Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA;6. Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA;7. Renal Division, Department of Medicine, Brigham and Women''s Hospital, Boston, MA 02115, USA;8. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA;9. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia;10. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA;11. Department of Pathology, Yale University, New Haven, CT 06520, USA;12. Case Western Reserve School of Medicine, Cleveland, OH 44106, USA;13. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA;14. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA;15. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;1. Academic Trials Promoting Team, Institut Jules Bordet and l''Université Libre de Bruxelles (ULB), Brussels, Belgium;2. Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center – IRCCS, Humanitas Cancer Center, Rozzano, Milan;3. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele - Milan, Italy;4. Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil;5. Unit of Clinical Epidemiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy;6. Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy;7. Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy |
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| Abstract: | Breast cancer (BC) is responsible for 14% of cancer-related deaths in women 1]. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of selective drugs, offering an effective and tolerable treatment. CDK4/6 inhibitors induce cell cycle arrest in the G1 phase, and may thereby prevent tumour progression. Three CDK4/6 inhibitors have been tested in clinical BC trials: palbociclib, ribociclib, and abemaciclib. The Food and Drug Administration (FDA) and European Commission (EMA) have approved palbociclib for the treatment of patients HR+ HER2- locally advanced or metastatic BC (aBC) in combination with an aromatase inhibitor as initial therapy in postmenopausal women or in combination with fulvestrant in women who have received prior endocrine therapy. Ribociclib has been approved by the FDA in combination with an aromatase inhibitor as initial therapy for postmenopausal women with HR+ HER2- aBC. Moreover, CDK4/6 inhibitors have shown promising results in the (neo)adjuvant setting. In this review, the principal completed and ongoing clinical trials in aBC are reviewed for both the metastatic as (neo)adjuvant setting. Tables will provide a complete overview of the ongoing clinical trials. At last, the future perspectives of these CDK4/6 inhibitors are discussed. |
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| Keywords: | Breast cancer Palbociclib Ribociclib Abemaciclib Cyclin-dependent kinase 4/6 CDK4/6 inhibition |
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