Assessment of Folate Receptor-alpha and Epidermal Growth Factor Receptor Expression in Pemetrexed-Treated Non-Small-Cell Lung Cancer Patients

作者：Christoph Daniel C; Reyna Asuncion Bernadette; Hassan Biftu; Tran Cindy; Maltzman Julia D; O' Shannessy Daniel J; Gauler Thomas C; Wohlschlaeger Jeremias; Schuler Martin; Eberhardt Wilfried E; Hirsch Fred R^*

来源：Clinical Lung Cancer, 2014, 15(5): 320-+.

DOI：10.1016/j.cllc.2014.05.002

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

Agents targeting the folate receptor-alpha (FRA) or epidermal growth factor receptor (EGFR) are approved by the US Food and Drug Administration or are in clinical development. FRA and EGFR expression in advanced nonesmall-cell lung cancer (NSCLC) was evaluated. In 160 advanced NSCLC patients, 47 patients (29%) had tumors expressing high levels of both receptors. This subgroup would be candidates for clinical trials studying combined targeted therapies. %26lt;br%26gt;Introduction: Folate receptor-alpha 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%26apos; 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 %26gt;= 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.

• 出版日期2014-9