Selecting patients with cyclooxygenase-2 (COX-2) expression by immunohistochemistry fails to improve survival outcomes in non-small cell lung cancer (NSCLC), according to research published in the Journal of Clinical Oncology (published online May 10, 2017; doi:10.1200/JCO.2016.71.3743).
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Tumor overexpression of COX-2 is associated with worse survival outcomes for patients with NSCLC. In a previous trial, selective treatment with COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC demonstrated improved progression-free survival (PFS) and overall survival (OS) in patients with moderate to high COX-2 expression by immunohistochemistry. A prospective study is needed to confirm this finding.
Martin J Edelman, MD, University of Maryland Greenebaum Cancer Center (Baltimore, MD), and colleagues conducted a double-blind, phase 3 trial to prospectively assess celecoxib’s effectiveness in improving survival outcomes. Researchers randomly assigned 322 patients with a COX-2 index of at least 2 to receive standard chemotherapy and either celecoxib (400 mg, twice daily) or placebo. The primary objective was to show improvement in PFS in patients with COX-2 index of at least 4 with a hazard ration of 0.645 with approximately 85% power at two-sided significance level of .05.
The study was discontinued for futility after 312 patients were randomly assigned.
Researchers found no significant differences in median PFS with a COX-2 index of at least 2 but less than 4 (5.16 vs 5.26 months; HR, 1.076; 95% CI, 0.853-1.367) or at least 4 (5.16 vs 5.45 months; HR, 1.046; 95% CI, 0.794-1.377) compared with placebo.
Additionally, there was no observable difference in median OS with a COX-2 index of at least 2 and less than 4 (13.4 vs 13.8 months; P = .1816) or at least 4 (10.8 vs 6.1 months; P = .1909) compared with placebo.
Subset analyses for histology, chemotherapy regimen, and incremental COX-2 expression did not exhibit any advantage for COX-2 inhibition.
Despite this being the first biomarker-driven trial in NSCLC in the US, authors of the study reported that the results ““failed to confirm that COX-2 inhibition in addition to standard chemotherapy treatment for patients who were selected by COX-2 expression could improve outcomes.” — Zachary Bessette
