CKD4/6 Inhibitors Found to Be Less Effective in Patients with HR+/HER2- Metastatic Breast Cancer with Bone-Only Metastases

Hormone receptor-positive (HR+) metastatic breast cancer has been found by clinical trials such as MONALEESA, MONARCH, and PALOMA to have improved progression-free survival (PFS) rates for patients with the use of CDK4/6 inhibitors (CDK4/6i) when combined with endocrine therapy. The most common site of metastases for patients with HR+ metastatic breast cancer is the bone, with approximately 40% of patients having only bone as the site of metastases. Bone-only disease has a more favorable outcome when compared to metastasis to other body sites, but clinical trials have not found significant improvement in PFS with use of CDK4/6i in bone-only disease patient-trial subsets.

To better understand the survival outcomes in patients with HR+ breast cancer with bone-only metastases, a retrospective study was conducted. Additionally, preclinical models of bone metastasis in breast cancer were used to evaluate CDK4/6i activity. The study examined records from 114 patients with HR+/HER2− metastatic breast cancer who received CDK4/6i in first- or second-line settings. Palbociclib combined with endocrine therapy for ≥2 months was given to all patients. There were 22 Black patients and 92 White patients in the study with a median age of 60 years. Bone-only disease was diagnosed in 47 patients and survival outcomes for these patients were compared to patients who had visceral only or bone and visceral metastatic lesions (BV group).

The median PFS for the bone-only group was 13.1 months and the BV group had a median PFS of 19.6 months. Multivariate analysis of the associated risk factors with PFS was performed. After adjusting for race and age, the bone-only disease groups had an hazard ratio of 1.62 (95% confidence interval; 1.04-2.54). For the 32 bone-only patients who received CDK4/6i as first-line treatment, the median PFS was 20 months compared with a median PFS of 28.4 months for the 43 patients in the BV group. When the clinical models were evaluated, single-agent ribociclib decreased primary mammary gland tumor burden, but the effect was abolished when CD8+ T-cells were depleted. When the bone colonization model was evaluated ribociclib was found to have little effect on the bone tumor burden. After ribociclib use in the primary tumor model Agr1+ immune suppressive macrophages were significantly decreased, but not in the bone tumor model.

Source:

Mardani, M, Noordeen S, Clifton K, et al. Clinical outcomes of CDK4/6 inhibitors in patients with bone only metastatic breast cancer. Poster presented at: San Antonio Breast Cancer Symposium. December 8, 2023; San Antonio, TX. Abstract # PO5-05-05.