TOPLINE:

In a cohort study of nearly 16,000 US patients with breast cancer who were prescribed a cyclin-dependent kinase (CDK) 4/6 inhibitor, only 46% underwent liver function testing in the 2 weeks before starting treatment. But most did undergo testing within 2 months of initiating therapy. 

METHODOLOGY:

• There are currently three CDK4/6 inhibitors approved for patients with hormone receptor (HR)-positive, HER2-negative breast cancer. Package inserts for two of these medications (abemaciclib and ribociclib) carry warnings about hepatotoxicity and recommend liver function testing before and during treatment. Labeling for the third, palbociclib, carries no such warning.
• To see how often testing is happening in practice, researchers used a US claims database covering patients with private or Medicare Advantage insurance. They included 15,958 patients with breast cancer (mean age, 58.5 years) who began CDK4/6 inhibitor therapy between February 2015 and August 2025.
• Liver function testing was estimated during three time periods: 2 weeks prior to treatment initiation, 1 day before or on the day of treatment initiation, and 60 days following treatment initiation. The researchers also identified cases of clinically significant acute liver injury (requiring inpatient diagnosis or procedure codes).

TAKEAWAY:

• Overall, 7333 patients (46%) had liver function tests in the 2 weeks prior to starting CDK4/6 treatment. Another 1891 (11.8%) underwent testing at treatment initiation. Those rates were similar regardless of which CDK4/6 inhibitor patients were prescribed.
• Most patients (80.9%) received liver function testing during the first 2 months of treatment. Among those tested after starting CDK4/6 therapy, the average time to the first test was 11.7 days (SD, 110.1 days).
• There were 49 incidents (0.3%) of acute liver injury in the 2 months following treatment initiation, with 37 (75.5%) occurring among patients who received liver function tests in the 2 weeks before treatment.
• The lack of difference in testing rates across the three CDK4/6 therapies suggests that package insert recommendations had limited impact on clinical practice, the study authors noted.

IN PRACTICE:

“Although liver function tests are commonly performed during treatment, this study found that a majority of patients initiating CDK4/6 therapies in the US did not receive liver function tests prior to treatment initiation as recommended in FDA-approved package inserts,” the authors wrote. They added that additional strategies, such as electronic health record prompts, may be needed to encourage timely testing.

SOURCE:

The study, led by Daniel C. Beachler, PhD, of Carelon Research in Wilmington, Delaware, was published as a research letter in JAMA Network Open.

LIMITATIONS:

The study was restricted to commercially insured patients, which may affect the generalizability of the findings. Claims-based data may be subject to coding inaccuracies and do not capture clinical factors that might influence liver function test ordering. 

DISCLOSURES:

Beachler and a co-author are employees of Carelon Research, a subsidiary of health insurer Elevance Health. Another co-author disclosed receiving grant funding for his institution from GSK during the conduct of the study, as well as consulting fees from several companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.