[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

Abstract

Introduction: Addition of cyclin-dependent 4/6 kinase (CDK4/6) inhibitors to endocrine therapy is standard of care in the treatment of women with advanced hormone receptor-positive HER2-negative breast cancer. However, the predictive factors for the treatment response to CDK4/6 inhibitor therapy are poorly elucidated. Early changes in the by [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake of tumors receiving different kinds of therapy have proven to reliably predict treatment outcomes in a variety of malignancies. Therefore, the feasibility of early metabolic response assessment to predict the long-term treatment response to CDK4/6 inhibitor therapy was evaluated in the present study.

Methods: Eight patients underwent FDG-PET/CT before and after the initiation of CDK4/6 inhibitor therapy (ribociclib, palbociclib or abemcaciclib). CDK4/6 inhibitor therapy was combined with either aromatase inhibition or fulvestrant. The median interval between the treatment start (including baseline PET) and the follow-up PET examination was 14 days. Conventional radiographic staging was performed 3 months after the start of CDK4/6 inhibitor therapy. The percentual changes in molecular tumor volume, SUVpeak, the summed SUVpeak of up to 5 metastases (PERCIST-5), and total lesion glycolysis (TLG) were calculated for each patient.

Results: Three patients showed progressive disease after 3 months of CDK4/6 inhibitor therapy, whereas 5 patients showed disease control (3 stable disease and 2 partial remission). Disease control was maintained in these patients (follow-up range 7-22 months). Patients with disease control had a significantly greater decline in TLG (-55.3 vs. 16.7%; p < 0.05). The same was true for the PERCIST-5 (-21.9 vs. 11.3%, p < 0.05). All patients with progressive TLG showed treatment failure and/or a poor outcome.

Conclusion: Elevated TLG on early FDG-PET seems to be associated with long-term treatment failure and a poor outcome in patients undergoing CDK4/6 inhibitor therapy for metastatic breast cancer. Early findings indicate a potential prognostic value of early FDG-PET in this setting and warrant a prospective evaluation.

Keywords: Breast cancer; Cyclin-dependent 4/6 kinase therapy; [18F]-fluorodeoxyglucose positron emission tomography-PET early metabolic response.