CDK4/6 Inhibitors in HER2-low Metastatic Breast Cancer

Human epidermal growth factor 2 (HER2-low) is increasingly thought to be a unique subtype of breast cancer. A sizable portion of patients who were previously classified as HER2-negativemay, in fact, be HER2-low. In patients with hormone receptor-positive (HR+)/HER2-negativemetastatic breast cancer, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are vital to treatment. A study to determine the clinical effectiveness of CDK4/6 in patients with HR+/HER2-negativemetastatic breast cancer enrolled participants from June 10, 2015, to December 28, 2022. The patients were followed until March 24, 2023. For this study, patients with immunohistochemistry (IHC) 0 were categorized as HER2–0 while those with IHC 1+ or IHC 2+/in situ hybridization negative by 2018 ASCO/CAP guidelines were categorized as HER2-low.

There were 239 patients enrolled in the study with 193 patients found to be HER2-low and 46 HER2–0 with no statistically significant clinicopathological characteristics between the 2 groups. There were 21 Black patients, 10 White patients, and 2 Asian patients in the HER2–0 cohort, with 13 patients reporting as “other” race. In the HER2-low cohort there were 86 Black patients, 35 White patients, and 11 Asian patients, with 54 patients reporting as “other” race and 7 unknown. Abemaciclib was received by 5 patients with HER2–0 metastatic breast cancer and 31 patients with HER2-low metastatic breast cancer. Palbociclib was given to 38 patients with HER2–0 metastatic breast cancer and 145 with HER2-low metastatic breast cancer while ribociclib was given to 3 patients with HER2–0 metastatic breast cancer and 17 patients with HER2-low metastatic breast cancer.

The median overall survival (OS) for HER2–0 patients was 36 months with a median progression-free survival (PFS) of 44 months. For HER2-low patients the OS was 34 months and PFS was 35 months. When HER2 status was further evaluated by multivariable analysis there was no statistically significant association between HER2-low status and worse OS or worse PFS. Analysis of HER2/CEP17 found a median of 1.25. The HER2 gene copy number (GCN) median was 2.58. The median OS for ratio-below patients was 25 months and the PFS for these patients was 35 months. For above-median patients, the median OS was 37 months and median PFS was 37 months. There was a significantly worse OS for patients with GCN-below-median but no significant difference in PFS.

Source:

Zhang F, Anampa Mesias J. Clinical effectiveness of CDK4/6 inhibitors in HER2-low metastatic breast cancer. Poster presented at: San Antonio Breast Cancer Symposium. December 6, 2023; San Antonio, TX. Abstract # PO1-05-10.