Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer.

INTRODUCTION: Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on treatment outcome of advanced non-small-cell lung cancer (NSCLC).

METHODS: We prospectively collected tissue samples, blood, and clinical data from two cohorts of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall survival (OS) and progression-free survival (PFS) to epidermal growth factor receptor (EGFR) TKIs and chemotherapy treatment.

RESULTS: BIM deletion polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.004). Among 120 patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.005). Multivariate analyses suggested that BIM deletion polymorphism was an independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p = 0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039).

CONCLUSIONS: BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS in advanced NSCLC.