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EGFR Variables Do Not Correlate With Response to Treatment With Gefitinib Plus Platinum-Based Chemotherapy

EGFR Variables Do Not Correlate With Response to Treatment With Gefitinib Plus Platinum-Based Chemotherapy

WILMINGTON, Delaware- Epidermal growth factor receptor (EGFR) variables "do not predict for survival benefits with gefitinib in combination with platinum-based chemotherapy," for non-small-cell lung can cer (NSCLC), according to Lisa Renee Bailey, PhD, MPH, of AstraZeneca, Wilmington, Delaware. Dr. Bailey was reporting on an analysis of two phase III trials showing that gefitinib (Iressa) combined with first-line platinumbased chemotherapy did not improve survival in NSCLC patients (abstract 7013). The study objectives were to determine whether EGFR is prognostic for survival, independent of treatment regimens, and whether it predicts outcomes for patients treated with gefitinib plus chemotherapy. "EGFR expression appears to be a prognostic factor but not a predictor of response to treatment," she said. "These results seem to contradict the belief in the literature." Tumor Samples Assessed Pretreatment tumor biopsies of 516 patients from the two trials that did not show a survival benefit (INTACT 1 and 2) were analyzed by immuno- histochemistry for EGFR. The percentage of tumor cells was assessed using four levels of intensity: no staining, 0; weak, 1+; moderate, 2+; strong, 3+; as well as the presence of complete membrane staining. A restricted backwards elimination Cox regression analysis was conducted to identify independent EGFR factors, and significant variables were also tested for treatment interaction to determine if they served as predictive factors. Dr. Bailey reported that two EGFR factors were prognostic for survival in patients treated with gefitinib and those receiving placebo. A glandular, rather than solid, tumor growth pattern and membrane staining were both associated with significantly longer survival. "Perhaps EGFR has a different role in early vs late disease?" Dr. Bailey suggested. Neither of these two variables was useful for predicting who would respond to gefitinib treatment. "Given the overall trial results for INTACT 1 and 2 showing no survival benefit between gefitinib and placebo, it was highly unlikely that EGFR variables would identify a subset of patients who receive survival benefit. The data presented support this hypothesis," Dr. Bailey concluded. She also pointed out that clinical use will require easier methods for measuring EGFR expression such as monoclonal antibodies or fluorescent in-situ hybridization (FISH) assays.

 
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