Significance of CEA Dynamics and Systemic Inflammatory Markers in HER2-Positive Metastatic Colorectal Cancer Patients Undergoing First-Line Chemotherapy: A Real-World Cohort Study

<i>Background and Objectives</i>: HER2-positive metastatic colorectal cancer (mCRC) represents a biologically distinct and clinically aggressive subtype associated with poor response to standard first-line chemotherapy. Reliable, low-cost prognostic biomarkers are urgently needed to identify early non-responders and guide treatment decisions. This real-world cohort study evaluated the prognostic value of carcinoembryonic antigen (CEA) kinetics and systemic inflammatory markers (SIMs) in HER2-positive mCRC treated with first-line chemotherapy. <i>Materials and Methods:</i> We retrospectively analyzed 98 patients with HER2-positive mCRC treated between 2015 and 2024. Serial CEA values were measured at baseline, after three cycles (week 6), and at radiologic progression. Early CEA change was categorized as ≥50% decline, 10-49% decline, or any increase. Baseline SIMs-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII)-were calculated from pretreatment blood counts. Progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox regression models. <i>Results</i>: Among patients with evaluable CEA kinetics (<i>n</i> = 60), early CEA increase occurred in 30% of patients (<i>n</i> = 18) and was strongly associated with inferior PFS (HR 2.84; 95% CI 1.81-4.44; <i>p</i> < 0.001). ROC analysis identified a ≥38% CEA reduction as the optimal predictor of radiologic response (AUC 0.79). High baseline NLR (≥3) and high SII (≥900) were also significantly associated with shorter PFS (median PFS: 5.2 vs. 9.1 months for NLR; 4.7 vs. 10.3 months for SII; both <i>p</i> < 0.01). In multivariate analysis, early CEA increase, high NLR, and high SII remained independent predictors of poor PFS. <i>Conclusions</i>: CEA dynamics and inflammation-based biomarkers provide robust, complementary prognostic information in HER2-positive mCRC. Early CEA increase is the strongest independent predictor of poor outcome, while high baseline NLR and SII further refine risk stratification. These inexpensive and widely accessible biomarkers may help identify early non-responders, optimize monitoring strategies, and support timely therapeutic adjustments in routine clinical practice.