Abstract PS1-12-15: Metabolic complete response on 18FDG-PET-CT is a key predictor of Progression-Free Survival in metastatic luminal breast cancer treated with CDK4/6 inhibitors (CDK4/6i)

Abstract Background: CDK4/6 inhibitors combined with endocrine therapy are the standard first-line treatment for HR+/HER2- metastatic breast cancer (MBC). However, predictive markers of treatment benefit remain limited. We hypothesized that 18F-FDG PET-CT may provide early prognostic insights in HR+/HER2- MBC. We evaluated the association between metabolic complete response (CMR) on PET-CT and progression-free survival (PFS) in patients treated with first-line CDK4/6 inhibitors and endocrine therapy. Methods: We conducted a retrospective cohort study including 95 patients with HR+/HER2- metastatic breast cancer (MBC) treated with first-line CDK4/6 inhibitors in combination with endocrine therapy between 2018 and 2023. All patients underwent serial 18F-FDG PET-CT scans to assess treatment response. Complete metabolic response (CMR) was defined as the complete absence of metabolic uptake on PET-CT at any point during first-line therapy, and patients were categorized as CMR or non-CMR. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). Survival analyses were performed using Kaplan-Meier estimates and Cox proportional hazards regression models to assess associations between metabolic response and clinical outcomes. Results: Among 95 patients, 60% achieved CMR. Median PFS was 35.06 months in CMR versus 23.89 months in non-CMR patients (p = 0.0004). The incidence rate of progression or death was lower in CMR patients (0.017 events per month) compared to non-CMR (0.035 events per month). CMR was independently associated with prolonged PFS (HR = 0.42; 95% CI: 0.256-0.688; p = 0.001). For OS, CMR also predicted better outcomes (HR = 0.062; 95% CI: 0.014-0.272; p = 0.0011), with a 5-year OS rate of approximately 95% in CMR patients versus 30% in non-CMR patients. In multivariate analysis, CMR remained the only independent predictor of survival, regardless of prior endocrine therapy, metastatic burden, or hormone receptor levels. Conclusions: Metabolic complete response on PET-CT strongly correlates with improved PFS and OS in HR+/HER2- MBC treated with first-line CDK4/6 inhibitors. PET-CT may serve as a valuable non-invasive prognostic biomarker to guide early treatment decisions in clinical practice. Citation Format: N. Soldi, V. Basílio, C. Machado, E. Carneiro, F. Balint, L. Gouveia, L. Leite, F. Makdissi, S. Sanches, A. Balieiro, V. de Lima, E. dos Santos. Metabolic complete response on 18FDG-PET-CT is a key predictor of Progression-Free Survival in metastatic luminal breast cancer treated with CDK4/6 inhibitors (CDK4/6i) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-12-15.