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Effects of Gefitinib on Serum Epidermal Growth Factor Receptor and HER2 in Patients with Advanced Non-Small Cell Lung Cancer

¹ Department of Oncology, Scientific Institute University Hospital San Raffaele, Milan; ² Laboratory of Clinical Research in Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan; ³ Division of Medical Oncology, Policlinico Monteluce, Perugia; and ⁴ Division of Medical Oncology, Bellaria Hospital, Bologna, Italy

ABSTRACT

Purpose: The aim of this study was to assess serum extracellular binding domains of epidermal growth factor receptor (EGFR) and HER2 as surrogate markers of Gefitinib (Iressa, ZD1839, AstraZeneca, London, United Kingdom) activity in patients with non-small cell lung cancer.

Experimental Design: Serum EGFR and HER2 levels were monitored in blood samples taken within 1 week of starting Gefitinib at day 28 and at every computed tomography scan evaluation. EGFR and HER-2 were assayed in duplicate using commercial sandwich enzyme-linked immunosorbent assay kits (Oncogene Science Bayer Corporation, Cambridge, UK). A logistic regression analysis was performed to evaluate: (1) the relationship between best overall tumor response and basal EGFR and HER2 levels, and (2) the association between best overall tumor response and the differences of EGFR and HER2 levels obtained at the best overall tumor response and at baseline.

Results: Forty-six pretreated patients were evaluated, including F/M:11/35, Eastern Cooperative Oncology Group performance status 0–1/2:39/7, IIIB/IV:11/35, and adenocarcinoma/nonadenocarcinoma 29/17. Five partial responses (11%) and 14 stable disease responses (30%) were observed. Median pretreatment EGFR and HER2 were 83.3 ng/ml and 13.7 ng/ml. For baseline EGFR and HER2, the odds ratio of progression was 0.95 [95% confidence interval (CI), 0.91–0.98; P = 0.01] and 0.87 (95% CI, 0.74–1.03; P = 0.11), respectively. The difference between the best overall tumor response and basal EGFR value was predictive for response with a 6% increase in the odds of progression for an increase of 1 ng/ml (odds ratio, 1.06; 95% CI, 1.01–1.11; P = 0.009) and for progression-free survival with a hazard ratio of 1.03 (95% CI, 1.01–1.04; P = 0.003).

Conclusion: Modifications of EGFR serum values during treatment seem to reflect Gefitinib activity.

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