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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. We therefore evaluated the efficacy of platinum-based chemotherapy in such patients.The efficacy of platinum-based chemotherapy was compared between patients with advanced nonsquamous NSCLC who harbor EML4-ALK and those who harbor epidermal growth factor receptor gene (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. Patients with EML4-ALK-positive tumors were significantly younger than wild-type patients. 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 one or three of the fusion gene were predominant and did not appear to differ in their sensitivity to the platinum-based regimens.In the absence of effective targeted therapy, patients with EML4-ALK-positive advanced NSCLC manifest an aggressive clinical course similar to that of those with wild-type tumors.