219P New prognostic factors in advanced HR+ HER2- breast cancer treated with CDK4/6 inhibitors

CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) represent the milestone of first-line therapy in hormone receptor-positive (HR+) HER2-negative (HER2-) metastatic breast cancer (mBC). Aim of our retrospective study was to identify new prognostic factors in this setting. All patients (pts) affected by HR+/HER2- mBC referred to our Institutions from February 2017 to August 2023 and treated with CDK4/6i + ET as first-line setting were included. 220 pts were included. Neutropenia occurred in 95.5% of pts, causing 38.2% of dose reduction and 4.1% of discontinuation. Median PFS (mPFS) was 35.2 months (m) (0.4-71.8). 10.0% of pts obtained complete response (CR), 46.8% partial response (PR), 32.7% disease stability (DS) and 10.5% disease progression (DP). At univariate analysis, mPFS was correlated to neutropenia (35.3m if present vs 9.8m if absent, p=0.0103), dose reduction (not reached (NR) if yes vs 26.2m if not, p=0.0002), treatment interruption (2.4m if yes vs 35.3m if not, p=0.0024) and disease response (NR if CR vs 37.1m if PR vs 35.2m if DS vs 4.3m if DP, p<0.0001). Only neutropenia was confirmed at multivariate analysis (p=0.0279). Median OS (mOS) was 4.3 years (y) (0.13-5.97) and was correlated with response (NR if CR vs 4.3y if PR vs 5.3y if DS vs 1.3y if DP) at univariate (p<0.0001) and multivariate (p=0.0445) analysis. Prognostic Nutritional Index (PNI) was prognostic for mPFS (47.3m if high vs 12.5m if low, p<0.0001) and for mOS (p=0.0006). Systemic Inflammation Index (SII) was prognostic for mPFS (47.3m if low vs 24.1m if high, p=0.0135), but not for mOS (p=0.053). mPFS was correlated to Neutrophil to Lymphocyte Ratio (NLR) at baseline (47.3m if low vs 24.1m if high, p=0.0019) and at better response (p=0.0023). mOS was correlated to baseline NLR (5.4y if low vs 3.4y if high, p=0.0173) and better response NLR (p=0.0179). mPFS was correlated to baseline Platelet-to-Lymphocyte Ratio (PLR) (47.3m if low vs 21.5m if high, p=0.0034) and DP PLR (15.8m if high vs 9.5m if low, p=0.0019), the latter confirmed at multivariate analysis (p=0.0166). Our study confirmed the efficacy of CDK4/6i in HR+ HER2- mBC, pointing out new prognostic factors as neutropenia, PNI, SII, PLR and NLR, of whom little data are present in literature.