Comparative analysis of overall survival of patient with non-small cell lung cancer harboring anaplastic lymphoma kinase fusion

Abstract

Background and purpose: The aim of this study was to examine the overall survival (OS) of patient with non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) fusion, who were treated in the pre-ALK inhibitor era and to compare the survival with a matched case cohort of ALK-wildtype (WT) patients.

Methods: Data from 1,166 stage IIIB/IV patients with non-squamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK FISH was performed on 262 cases that were either EGFR wild-type (WT) or non-responders to prior EGFR tyrosine kinase inhibitor (TKI) therapy. Survival analysis was conducted to compare the OS between 3 groups: 1) ALK fusion-positive, 2) EGFR mutation-positive and 3) ALK-WT/EGFR-WT (WT/WT). Progression-free survival (PFS) of 1st-line platinum-based doublet chemotherapy and EGFR TKIs was also analyzed.

Results: Twenty-three cases were ALK fusion-positive by FISH and did not receive ALK inhibitors during the follow-up period. The median OS of ALK fusion-positive, EGFR mutation-positive and WT/WT patients was 12.2, 29.6, and 19.3 months, respectively (P-value

vs. EGFR mutation-positive: 0.001, vs. WT/WT: 0.127). The PFS of 1st-line platinum-based chemotherapy for the 3 groups was not different. However, the PFS of EGFR TKIs was shorter in ALK fusion-positive patients, compared with the other two groups (P-value

vs. EGFR mutation-positive: < 0.001, vs. WT/WT: 0.021).

Conclusion: Before the introduction of ALK inhibitors, ALK fusion-positive patients experienced the shortest survival, albeit not statistically different from WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK fusion-positive patients were even more resistant to EGFR TKI treatment than were WT/WT patients.