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https://doi.org/10.1158/0008-5472.sabcs-09-3095
Copy DOIJournal: Cancer Research | Publication Date: Dec 15, 2009 |
Abstract Background: Lapatinib (L) is a potent and selective dual inhibitor of EGFR and HER2. In HER2 positive metastatic breast cancer (MBC) pretreated with trastuzumab-based therapies, the association of L + Capecitabine (C) showed superior response rate (RR) and progression free survival (PFS) over C alone. We analyzed the correlation between EGFR gene copy number and clinical outcome in a population undergoing treatment with L 1250 mg daily plus C 2000 mg/m2 days 1-14 every 21. Materials and methods: EGFR gene copy number was assessed by FISH analysis in paraffin-embedded tissue blocks from 30 HER2 positive patients who had failed at least one trastuzumab-based therapy in the metastatic setting. EGFR gene status was scored as: the mean value of EGFR gene copy number (GCN) per nucleus, the mean ratio between EGFR and Chromosome 7 and the percentage of cells displaying more than 5 EGFR GCN. A receiver operating characteristic (ROC) analysis was set up to define the cut-off of mean EGFR GCN. A value greater than 3.36 was able to discriminate responders versus non-responders. The primary end point of the study was identification of the EGFR FISH score that best predicts RR Results: Twenty-five patients were evaluable for EGFR FISH analysis. No sample displayed a homogeneous amplification of the EGFR gene by ratio (EGFR gene/CEP 7 ≥2). Patients characteristics were as follows: median age 52.4 (range 32-70), visceral disease in 20 patients (80%), brain metastases in 11 patients; median number of previous trastuzumab-based therapies was 2 (1-4). Twelve patients achieved a partial response for a RR of 48% (95% CI: 28.8-64.5). At a median follow up of, PFS was 7 months (95%CI: 5-8). Median overall survival has not been reached at the time of analysis. Mean EGFR GCN was > 3.36 in 10/25 patients. These patients showed a significantly higher RR (n=8/10; 80%) as compared to those with mean EGFR GCN ≤3.36 (n= 4/15; 27%), (p=0.009). No significant difference in terms of PFS was seen. Conclusion: high EGFR GCN might predict for an increased likelihood of responding to L. This is the first report associating increased EGFR GCN with sensitivity to L. These results warrant further investigation on a larger sample of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3095.
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