Ribociclib for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

ABSTRACT

Introduction: The emergence of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors marked a significant advancement in the treatment of advanced breast cancer. Ribociclib is an orally bioavailable, highly selective inhibitor of CDK4/6. In combination with various endocrine therapies, ribociclib has demonstrated clinical activity as a first-line therapy for patients with HR+, HER2− advanced breast cancer, without compromising the favorable toxicity profile associated with endocrine therapy. Thus, ribociclib is now considered a new standard of care for HR+, HER2− advanced breast cancer.

Areas covered: This review provides a concise overview of the preclinical and clinical development of ribociclib, including evidence of its clinical activity and safety profile when combined with endocrine therapy in HR+, HER2− advanced breast cancer.

Expert commentary: CDK4/6 inhibition represents a promising treatment option for patients with HR+ metastatic breast cancer. Ribociclib significantly improved progression-free survival in patients receiving first-line endocrine therapy for HR+, HER2− advanced breast cancer. Planned and ongoing trials investigating ribociclib in combination with other endocrine therapies and in various clinical settings will help to determine the optimal treatment sequence for different patient populations.

KEYWORDS:

• Breast cancer
• cyclin-dependent kinase
• CDK4/6
• hormone receptor-positive
• inhibitors of cyclin-dependent kinase 4/6 proteins
• LEE011
• letrozole
• ribociclib

Acknowledgment

Medical writing assistance was provided by Bhavika Modasia PhD of Articulate Science Ltd.

Declaration of interest

Since 2016, Dr. Burris reports grants to his institution, Sarah Cannon Research Institute, from Novartis during the conduct of the study and pertaining to the submitted work. Dr. Burris reports grants to his institution for studies on which he served as Principal Investigator outside of the submitted work from the following companies: Acerta Pharma, Agios, Array BioPharma, AstraZeneca, Amplimmune, BioMed Valley Discoveries, Inc., BioAtla, eFFECTOR Therapeutics Eli Lilly, Genentech, CicloMed, Immunocore, Intellikine, Janssen, Loxo Oncology, MacroGenics, MedImmune, Novartis, Pfizer, Cytomx, Seattle Genetics, Stem CentRx, Tesaro, TG Therapeutics, Verastem, Vertex Pharmaceuticals, Bristol Myers Squibb, Gilead, Harpoon Therapeutics, Hengrui Therapeutics, Jounce Therapeutics, Exelixis; Merck, Moderna, Revolution Medicines, Amplimmune, Celgene, Clovis Oncology, GlaxoSmithKline, Mirna Therapeutics and Takeda. Dr. Burris reports consulting fees paid for his services to his institution from the following: AstraZeneca, Janssen Medimmune, Novartis, Bristol Myers Squibb, Celgene, Hoffman LaRoche, Tolero, Eisai, Boehringer Ingelheim, and Forma. Dr. Burris reports, non-financial support to his institution from Hoffman LaRoche, Merck, Tesaro, Novartis, Millennium, Lilly, AsttraZeneca. Dr. Burris reports expert witness fees for his services paid by Novartis to his institution.

Additional information

Funding

This manuscript has received funding from Novartis Pharmaceuticals Corporation.