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Clin Lung Cancer. 2014 Sep;15(5):320-30.e1-3. doi: 10.1016/j.cllc.2014.05.002. Epub 2014 Jun 3.

Assessment of folate receptor-α and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients.

Author information

  • 1Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO.
  • 2Morphotek Inc, Exton, PA.
  • 3Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 4Department of Pathology and Neuropathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 5Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. Electronic address: fred.hirsch@ucdenver.edu.

Abstract

INTRODUCTION:

Folate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed.

PATIENTS AND METHODS:

Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS).

RESULTS:

Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076).

CONCLUSION:

Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Antifolate chemotherapy; Combination of targeted agents; Correlation of receptor expression; Predictive biomarker; Therapeutic antibody

PMID:
24993594
[PubMed - in process]
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