Keith A Hecht1, Christopher Selby2. 1. 1 Southern Illinois University Edwardsville School of Pharmacy, IL, USA. 2. 2 Texas Tech University Health Sciences Center, Dallas, TX, USA.
Abstract
OBJECTIVE: To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor-positive advanced breast cancer (ABC). DATA SOURCES: A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. STUDY SELECTION AND DATA EXTRACTION: Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. DATA SYNTHESIS: Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor-positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor-positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. CONCLUSIONS: The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.
OBJECTIVE: To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor-positive advanced breast cancer (ABC). DATA SOURCES: A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. STUDY SELECTION AND DATA EXTRACTION: Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. DATA SYNTHESIS: Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor-positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor-positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. CONCLUSIONS: The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.
Entities:
Keywords:
abemaciclib; breast cancer; cyclin-dependent kinase; palbociclib; ribociclib
Authors: Mariane Teodoro Fernandes; Jacob J Adashek; Carmelia Maria Noia Barreto; Ana Cláudia Barbin Spinosa; Barbara de Souza Gutierres; Gilberto Lopes; Auro Del Giglio; Pedro Nazareth Aguiar Journal: Drugs Context Date: 2018-11-05