Anaplastic lymphoma kinase gene rearrangement predicts better prognosis in NSCLC patients: A meta-analysis.

OBJECTIVE: For non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutations are predictive markers of the treatment benefit from selective tyrosine kinase inhibitors (TKI). However, their prognostic roles remained uncertain. Thus, we conducted this meta-analysis to evaluate the prognosis of ALK+ NSCLC patients in the treatment of surgery, chemotherapy, and/or EGFR-TKI.

MATERIALS AND METHODS: PubMed, Embase and Cochrane databases were thoroughly searched to identify relevant studies. Primary endpoints of this study included overall survival (OS), recurrence/progression free survival (RFS/PFS) and objective response rate (ORR). All statistical analyses were performed via REVIEW MANAGER (version 5.3).

RESULTS: In total, 15 studies involving 4981 NSCLC patients were included. This study demonstrated that smoking status profoundly influenced prognosis of ALK related NSCLC. In the general population with NSCLC, compared with ALK- arm, ALK+ arm obtained a significantly better prognosis (HR=0.81 for OS, 95% CI=0.72-0.91; 0.80 for RFS/PFS, 95% CI=0.70-0.90), even after further stratification analysis according to disease stage. However, in the non-smoking population with NSCLC, compared with ALK- arm, those in the ALK+ arm had a worse prognosis (HR=1.65 for OS, 95% CI=1.28-2.12; 1.23 for RFS/PFS, 95% CI=1.05-1.44). Furthermore, ALK+ patients experienced a significantly higher ORR in pemetrexed-based chemotherapy but not in EGFR-TKI.

CONCLUSIONS: Smoking status had a profound influence on the ALK-related prognosis of NSCLC. ALK rearrangement predicted a better prognosis in the general population with NSCLC, but a poor survival in the non-smoking population. Therefore, stratification according to smoking status is strongly recommended for future studies exploring ALK-related prognosis.