Reference Detail

Ref Type

Journal Article

PMID

(28351928)

Authors

Tripathy D, Bardia A, Sellers WR

Title

Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	23	13	2017 Jul 01	3251-3262	Clin Cancer Res

URL

Abstract Text

The cyclin D-cyclin-dependent kinase (CDK) 4/6-p16-retinoblastoma (Rb) pathway is commonly disrupted in cancer, leading to abnormal cell proliferation. Therapeutics targeting this pathway have demonstrated antitumor effects in preclinical and clinical studies. Ribociclib is a selective, orally bioavailable inhibitor of CDK4 and CDK6, which received FDA approval in March 2017 and is set to enter the treatment landscape alongside other CDK4/6 inhibitors, including palbociclib and abemaciclib. Here, we describe the mechanism of action of ribociclib and review preclinical and clinical data from phase I, II, and III trials of ribociclib across different tumor types, within the context of other selective CDK4/6 inhibitors. The pharmacokinetics, pharmacodynamics, safety, tolerability, and clinical responses with ribociclib as a single agent or in combination with other therapies are discussed, and an overview of the broad portfolio of ongoing clinical trials with ribociclib across a wide range of indications is presented. On the basis of the available data, ribociclib has a manageable tolerability profile and therapeutic potential for a variety of cancer types. Its high selectivity makes it an important partner drug for other targeted therapies, and it has been shown to enhance the clinical activity of existing anticancer therapies and delay the development of treatment resistance, without markedly increasing toxicity. Ongoing trials of doublet and triplet targeted therapies containing ribociclib seek to identify optimal CDK4/6-based targeted combination regimens for various tumor types and advance the field of precision therapeutics in oncology. Clin Cancer Res; 23(13); 3251-62. ©2017 AACR.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	melanoma	sensitive	Encorafenib + Ribociclib	Phase Ib/II	Actionable	In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928).	28351928