Circulating Tumor Cells Predict Prognosis Following First-Generation EGFR-TKI Treatment in EGFR- and TP53-Mutant Non-Small Cell Lung Cancer

Purpose: First-generation EGFR-TKIs have become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. This study isolates and quantifies circulating tumor cells (CTCs) and evaluates patient prognosis before and after first-line treatment with EGFR-TKIs in advanced NSCLC with EGFR and TP53 mutation. Methods: : Patients with advanced NSCLC with EGFR and TP53 mutation were treated with a first-generation EGFR-TKI using a standard daily dose. Continuous blood samples were collected at baseline (CTCs-d0) and 28 days (CTCs-d28), and the isolation by size of tumor cells (ISET) method was used to detect CTCs. Results: : The CTC results were divided into favorable (< 5 CTCs) and unfavorable (≥ 5 CTCs) groups. The median progression-free survival (PFS) of patients in the favorable group was significantly longer at baseline compared to those in the unfavorable group (15 vs 7.5 months; p = 0.0055). After 28 days of treatment with first-generation EGFR-TKI, the PFS of patients in the favorable group was 12.5 months, which was significantly longer than the median PFS of 7 months in the unfavorable group (p = 0.0003). After treatment, the PFS of patients with reduced CTCs was significantly better than those with no significant change in CTCs (9 months vs 6 months, p = 0.014). In univariate and multivariate analysis, patients with CTCs-d0 ≥ 5 and CTCs-d28 ≥ 5 had significantly lower PFS when compared to those with CTCs-d0 < 5 and CTCs-d28 < 5, respectively. Conclusion: This study confirmed for the first time that CTC count is closely correlated with prognosis in EGFR- and TP53-mutant advanced NSCLC following first-line treatment with first-generation EGFR-TKIs.