Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio for EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients Treated with First-Line EGFR-TKIs: A Large Population-Based Study and Literature Review

BACKGROUND: Resistance inevitably develops in epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients after treatment of EGFR tyrosine kinase inhibitors (EGFR-TKIs). The albumin-to-alkaline phosphatase ratio (AAPR), a novel index, has been reported to be associated with survival in various cancers. In this study, we explored the prognostic value of AAPR in EGFR-mutated advanced NSCLC patients treated with first-line EGFR-TKIs. METHODS: The clinical and pretreatment laboratory data were retrospectively extracted from hospital medical system. The Log-rank and Kaplan–Meier analyses were adopted to detect differences in survival between groups. Univariate and multivariate Cox’s proportional hazard regression models were applied to assess the prognostic value of AAPR for progression-free survival (PFS) and overall survival (OS). RESULTS: Totally, 598 EGFR-mutated NSCLC patients with stage IIIB-IV were enrolled into this study. The median age of all patients was 60 years, and 56.9% were women. About 97% patients had common EGFR gene mutations of deletions in exon 19 (19 del) or a point mutation in exon 21 (L858R). Using receiver operating characteristic (ROC) curve analysis and the Youden index, the optimal cut-off value of pretreatment AAPR was 0.47. Patients with high AAPR achieved longer median PFS and OS than patients with low AAPR (14.0 months vs 10.4 months, P<0.01; 58.2 months vs 36.7 months, P<0.001, respectively). The multivariate analysis by Cox’s proportional hazards regression model demonstrated that AAPR was an independent prognostic factor for both PFS (HR: 0.813, 95% CI: 0.673–0.984, P=0.033) and OS (HR: 0.629, 95% CI: 0.476–0.830, P=0.001). CONCLUSION: Pretreatment AAPR, measured as part of routine blood biochemical test, may be a reliable prognostic indicator in EGFR-mutated advanced NSCLC patients treated with first-line first-generation EGFR-TKIs.