For patients with HR+/ERBB2 (formerly HER2-) metastatic breast cancer, CDK4/6 inhibitors, and endocrine therapy has become a more common treatment option. A recent study looked at several key outcomes, including overall survival and progression-free survival when comparing the combination treatment to endocrine therapy alone.  Results of the study were published in JAMA Open Network.

The researchers reviewed 472 records, which was reduced to 16 articles after meeting various inclusion criteria. The researchers then focused on nine studies following exclusion criteria. The nine studies included more than 5,000 patients. 

According to the researchers, the addition of CDK4/6 inhibitors was associated with a benefit to overall survival (HR, 1.33; 95% CI, 1.19-1.48; P<.001) compared to endocrine therapy alone. The combination also showed better results in several subgroups, including first-line (HR, 1.35; 95% CI, 1.18-1.54; P<.001) and second-line (HR, 1.30; 95% CI, 1.09-1.54; P<.001) therapy and pre (HR, 1.32; 95% CI, 1.04-1.66; P<.001) and postmenopausal women (HR, 1.34; 95% CI, 1.18-1.52; P<.001).

The combination also provided better results for progression-free survival benefit (HR, 1.84; 95% CI, 1.70-1.98; P<.001) and objective response rate benefit (odds ratio, 2.02; 95% CI, 1.61-2.53; P<.001). 

Despite the positive findings, the authors noted that the combination was also associated with significantly increased risk of grade 3 or 4 adverse events, including neutropenia (HR, 57.05; 95% CI, 38.26-85.05; P<.001), leukopenia (HR, 36.36; 95% CI, 19.35-68.34, P<.001), and diarrhea (HR 4.97; 95% CI, 2.84-8.69; P<.001). 

An editorial reviewing the study noted that there is currently an effort to use biomarkers to predict the response to CDK4/6 inhibitors. While several recent studies have attempted to find such a connection, the authors noted those efforts have not yet proven effective. 

“Currently, there are no biomarker data to suggest avoidance of a CDK4/6 inhibitor for a particular group of patients,” the authors of the editorial said. “These data are hypothesis-generating and are not currently recommended to guide clinical care.”  

As more is learned about the treatment, the authors said providers should continue to discuss the potential benefits of CDK4/6 inhibitors with patients with this particular form of cancer.