Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy

The EML4-ALK fusion oncogene represents a recently identified molecular target in a subset of patients with non-small-cell lung cancer (NSCLC). Limited data have been available, however, on the outcome of first-line platinum-based chemotherapy in patients with EML4-ALK-positive advanced NSCLC who have not been treated with an ALK kinase inhibitor. The efficacy of platinum-based chemotherapy was compared between patients with advanced nonsquamous NSCLC who harbor EML4-ALK and those who harbor EGFR mutations and those with neither molecular abnormality. Among 200 patients with advanced nonsquamous NSCLC, 18 (9.0%) were positive for EML4-ALK, 31 (15.5%) harbored EGFR mutations, and 151 (75.5%) were wild type for both abnormalities. Platinum-based combination chemotherapy showed similar efficacies in the EML4-ALK, EGFR mutation, and wild-type cohorts in terms of response rate and progression-free survival, and overall survival in the EML4-ALK cohort closely resembled that in the wild-type cohort. Within the EML4-ALK cohort, patients with variants 1 or 3 of the fusion gene were predominant and did not appear to differ in their sensitivity to the platinum-based regimens. Patients with EML4-ALK-positive advanced NSCLC manifest an aggressive clinical course similar to that of those with wild-type tumors if the effective targeted therapy is not instituted.