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CDK4/6 Inhibitors Continue to Offer Hope in Breast Cancer

Angelica Welch
Published: Friday, Jul 06, 2018

Jacqueline Vuky, MD

Jacqueline Vuky, MD

CDK4/6 inhibitors have excited the field of advanced breast cancer with 3 FDA approvals in the last 3 years. The introduction of this class of agents has allowed for additional therapeutic options, including more combination therapy, said Jacqueline Vuky, MD.

Palbociclib (Ibrance) received an accelerated approval from the FDA in 2015 for use in combination with letrozole as a frontline treatment for postmenopausal women with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer. This approval was converted to a full approval by the FDA in March 2017. This CDK4/6 inhibitor is now indicated for use in combination with other aromatase inhibitors (AIs) in this setting.

The second CDK4/6 inhibitor to be approved in breast cancer was ribociclib (Kisqali), which is indicated for use in combination with an AI for the frontline treatment of postmenopausal women with hormone receptor (HR)–positive, HER2-negative advanced breast cancer. In January 2018, this agent was also granted a breakthrough designation for use in combination with tamoxifen or an AI in patients with pre- or perimenopausal HR-positive, HER2-negative breast cancer.

In February 2018, abemaciclib (Verzenio) was approved in combination with an AI for the frontline treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. In September 2017, the agent was approved for use in combination with fulvestrant following progression on endocrine therapy. It was also approved as a single agent for patients who had received endocrine therapy and chemotherapy.

Vuky, associate professor of medicine, School of Medicine, Oregon Health and Science University, discussed the management of metastatic disease and CDK4/6 inhibitors in breast cancer during an interview at the 2018 OncLive® State of the Science Summit™ on Breast Cancer.

OncLive: Can you give an overview of your presentation on CDK4/6 inhibitors? 

Vuky: CDK4/6 inhibitors are very exciting. We haven't had a breakthrough with endocrine therapy for metastatic disease, or even early-stage disease, for a while. What is exciting about these is that the trials are designed very rationally. For a long time now, we have been trying combinations with endocrine therapy and therapeutic targets. The fact that this is the first combination that has changed median progression-free survival (PFS) is very exciting for our patients. Giving them more options is why we do clinical research and take care of patients. 

How does multiple approvals of CDK4/6 inhibitors impact treatment for these patients?

Much like with other therapies, such as VEGF inhibitors or mTOR inhibitors, it is exciting that we do have choices, but it does seem that each one is a little different. Although the data show good efficacy as well as median PFS, the fact that they have different side effects and schedules, and even different abilities to bind to CDK4/6, is pretty exciting. We like choices. Although, we do have to be concerned about the price of all of these drugs. Still, from a patient care standpoint, it is very exciting to have all of these choices.

If a patient progresses on a CDK4/6 inhibitor, is there rationale to move them to another?

As you know, there are no data yet. Once these new drugs come out, we can basically use them the way that we want to. However, we would like to have more data. Right now, we do not really know. In my practice, I have given sort of a second-line CDK4/6 inhibitor, and that is abemaciclib because it has single-agent activity. I would not say that there is a mass experience out there, I am not aware of a trial that addresses that at this point.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: How Do We Leverage PARP Inhibition Strategies in the Contemporary Treatment of Breast Cancer?May 31, 20191.5
Community Practice Connections™: A Better Way to Stop Pain: Paths Toward Responsible Postsurgical Pain Management for Patients With Breast CancerMay 31, 20191.5
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