Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy
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Published on: February 12, 2017
Background:
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.
Patients And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
First-line platinum chemotherapy shows similar efficacy in advanced non-small-cell lung cancer (NSCLC) patients with EML4-ALK fusions, EGFR mutations, or neither. EML4-ALK positive NSCLC patients without targeted therapy face an aggressive clinical course.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The EML4-ALK fusion oncogene is a molecular target in a subset of non-small-cell lung cancer (NSCLC) patients.
- Limited data exist on the efficacy of first-line platinum-based chemotherapy in EML4-ALK-positive advanced NSCLC patients who have not received ALK inhibitors.
Purpose of the Study:
- To compare the efficacy of first-line platinum-based chemotherapy in advanced nonsquamous NSCLC patients with EML4-ALK fusions versus those with EGFR mutations or wild-type tumors.
Main Methods:
- Retrospective analysis of 200 advanced nonsquamous NSCLC patients.
- Comparison of chemotherapy efficacy (response rate, progression-free survival, overall survival) among EML4-ALK positive, EGFR mutation positive, and wild-type cohorts.
Main Results:
- 18% (9.0%) of patients were EML4-ALK positive, 31% (15.5%) had EGFR mutations, and 151% (75.5%) were wild type.
- Platinum-based chemotherapy demonstrated similar efficacy across all three groups.
- Overall survival in the EML4-ALK cohort was comparable to the wild-type cohort.
- EML4-ALK variants 1 and 3 were predominant and showed similar sensitivity to platinum regimens.
Conclusions:
- Patients with EML4-ALK-positive advanced NSCLC have an aggressive clinical course comparable to wild-type tumors when effective targeted therapy is not administered.