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.