CDK4/6 Inhibitors Make Impact in HR-Positive Metastatic Breast Cancer

Christin L. Melton, ELS
Published: Tuesday, Dec 19, 2017
Adam M. Brufsky, MD, PhD

Adam M. Brufsky, MD, PhD
The introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors has resulted in a significant paradigm shift in the treatment of hormone receptor–positive breast cancer, helping to make the new agents part of rapidly developing improvements in personalized care for patients, according to an OncLive® Peer Exchange panel of experts.

CDK4/6 inhibitors, a category that currently consists of 3 FDA-approved agents, has taken the “estrogen receptor (ER)-positive part of the metastatic breast cancer world by storm,” noted Adam M. Brufsky, MD, PhD, who served as moderator of the program.

Anti-CDK4/6 Agents

Cyclin family proteins activate CDKs to help regulate cell cycle progression.1 More than 50% of women with breast cancer have alterations in the cyclin D/CDK/retinoblastoma (Rb) pathway that cause overexpression of cyclin D, a protein family implicated in disease pathogenesis and progression.1 Studies have also documented overexpression of other cyclins and of CDK4.1 “Cyclin D is an important transcriptional product of the ER,” said panel member Joyce A. O’Shaughnessy, MD. In women with ER-positive breast cancer, amplification of cyclin D is associated with poor response to standard endocrine therapies,1 especially in women with luminal B tumors, O’Shaughnessy said. “Our endocrine agents, even really good aromatase inhibitor inhibition or really good degradation of ER, are still not perfect in terms of totally clamping down on that pathway,” she said.

The European Medicines Agency has approved palbociclib and ribociclib, while abemaciclib remains under consideration. “We were waiting… for this kind of drug for more than 10 years because in the era of endocrine treatment of breast cancer patients, the last innovation has been aromatase inhibition ...I’m very happy to have these drugs on the market,” said Michael Untch, MD.

New First-Line Therapies

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