CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status: A Real-World Evidence Study

There are little data on real-world treatment patterns and the efficacy of cyclin-dependent kinase (CDK)4/6 inhibitors in germline BRCA mutation–positive breast cancer. Adults with hormone receptor (HR)-positive, HER2-negative, metastatic breast cancer treated with CDK4/6 inhibitor therapy were retrospectively identified from the Flatiron Health Analytics database between 2013 and 2018. Patients with known germline BRCA status were divided into 2 groups: BRCA mutation–positive and BRCA wild-type. From the time of initiation of the first line of therapy with a CDK4/6 inhibitor, overall survival and the time to first subsequent therapy or death were calculated.¹

Of the 2968 patients with HR-positive, HER2-negative metastatic breast cancer who were treated with a CDK4/6 inhibitor, 28.9% had known germline BRCA status, with 9.9% having BRCA mutation–positive disease and 90.1% having BRCA wild-type disease.¹

Metastatic breast cancer is treatable but not curable. Surgical and radiation therapy, as well as hormone therapy, chemotherapy, targeted medicines, or a combination of these therapies may be indicated depending on the metastatic breast cancer subtype. Targeted cancer therapies affect specific oncogenic molecular pathways and have shown significant clinical effectiveness in patients with metastatic breast cancer, generally with a lower toxicity profile than traditional toxic chemotherapy.²

Although various medicines have been developed to target HER2, they are only appropriate for the approximately 20% of patients with breast cancer who have HER2-positive disease. CDK4/6 inhibitors are a form of targeted therapy used to treat HR-positive, HER2-negative metastatic breast cancer, which accounts for approximately 68% of all female breast malignancies. In February 2015, the first CDK4/6 inhibitor, palbociclib, was licensed in the United States for the treatment of patients with HR-positive, HER2-negative metastatic breast cancer, followed by ribociclib and abemaciclib in 2017.² Oral oncolytics such as CDK4/6 inhibitors are preferred by some patients over injections and infusions for a variety of reasons, including convenience, improved sense of control, and fewer injection-site problems. While oral oncolytics have some benefits, patient self-administration of oral therapy shifts medication management from healthcare providers to patients, potentially raising concerns about patients’ ability and willingness to adhere to a prescribed regimen as directed by their healthcare provider or to take them for the prescribed duration.²

This finding emphasizes the unmet need for better treatment selection and sequencing in patients with germline BRCA mutation–positive disease. Larger samples of patients who have had biomarker testing should be studied in the future.¹

References

1. Collins JM, Nordstrom BL, McLaurin KK, et al. A real-world evidence study of CDK4/6 inhibitor treatment patterns and outcomes in metastatic breast cancer by germline BRCA mutation status. Oncol Ther. 2021;9:575-589.
2. Stephenson JJ, Gable JG, Zincavage R, et al. Treatment experiences with CDK4&6 inhibitors among women with metastatic breast cancer: a qualitative study. Patient Prefer Adherence. 2021;15:2417-2429.