Abemaciclib shows small benefit after a prior CDK 4/6 inhibitor stops working | ASCO 2024

Background

CDK 4/6 inhibitors have been game changers in breast cancer treatment. They are now part of the standard first treatment for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

Three CDK 4/6 inhibitors have been approved by the FDA and continue to be studied—in different combinations and sequences—for early-stage, advanced, and metastatic disease: abemaciclib, palbociclib (Ibrance), and ribociclib (Kisqali). Abemaciclib is the only one of the three that is approved for early-stage breast cancer and the only one approved to be used alone against advanced or metastatic breast cancer. It is taken in pill form. Its side effects are generally mild.

When combined with endocrine therapy, these drugs often extend time without cancer growth or spread. After a while, though, they can stop working. When this happens, the next step is to try another targeted therapy, typically one that requires biomarker testing to determine eligibility. The next therapy is seldom very effective, often delaying cancer growth for six months or less. People whose tumors do not test positive for other biomarkers have even more limited options.

One area of study focuses on switching CDK 4/6 inhibitors: does it make sense to try another CDK 4/6 after one stops working? The results presented here provide new insight into this question.

Results

People who received abemaciclib plus fulvestrant after another CDK 4/6 inhibitor drug stopped working went longer without cancer growth than those who received only fulvestrant. The postMONARCH phase III clinical trial included 368 people who had prior CDK 4/6 treatment. Most had taken palbociclib previously (59%), compared to ribociclib (33%) and abemaciclib (8%).

Participants in the abemaciclib-plus-fulvestrant group went six months without cancer progressing compared to 5.3 months for those in the fulvestrant-only group, a 27% lower risk of cancer growing or spreading. The benefit was seen across subgroups and was strongest in people who had received a CDK 4/6 inhibitor and endocrine therapy as a first-line treatment, with even better results in people who had been on the first CDK 4/6 drug for a longer period. Also likely to benefit from abemaciclib in this situation:

• People without cancer in the liver or lungs
• People with tumor or mass large enough to be measured

Participants had regular scans to monitor progress. All test results were read by both the patient’s doctor and an independent reviewer. The results were even stronger when determined by independent review; the addition of abemaciclib led to a 45% lower risk of cancer growing or spreading.

Even though the overall difference in these results was modest, the data confidence is strong. Importantly, this study suggests that switching CDK 4/6 inhibitors can have a positive effect, opening up a new possible treatment option for people with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

What does this mean for you?

If you have advanced or metastatic breast cancer and a CDK 4/6 inhibitor stopped working for you, you may benefit from trying another CDK 4/6 inhibitor, especially if the cancer does not match with other targeted therapies. This study focused on abemaciclib. A similar phase II study of ribociclib also had positive results. Ask your doctor about options.