The impact of the ALK fusion variant on clinical outcomes in EML4-ALK patients with NSCLC: a systematic review and meta-analysis

Background: Recent studies showed that ALK-fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies showing no correlation between ALK variants and prognoses. Methods: A systematic review and meta-analysis was performed to evaluate the prognostic value of EML4-ALK fusion variants for patient outcomes. Results: 28 studies were included in the analysis. According to the pooled results, patients harboring variant 1 showed equivalent progression-free survival (PFS) and overall survival (OS) with non-v1 patients (hazard ratio [HR] for PFS: 0.91 [0.68-1.21]; p = 0.499; OS: 1.12 [0.73-1.72]; p = 0.610). Similarly, patients with v3 showed the same disease progress as non-v3 patients (pooled HR for PFS = 1.07 [0.72-1.58]; p = 0.741). However, pooled results for OS suggested that patients with v3 had worse survival than non-v3 patients (HR = 3.44 [1.42-8.35]; p = 0.006). Conclusion: Results suggest that patients with v1 exhibited no significant difference from non-v1 in terms of OS and PFS, while v3 was associated with shorter OS in ALK-positive patients with non-small cell lung cancer.