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15.11.2005 – 17:04

AstraZeneca GmbH

New Data Highlight Increased EGFR Gene Copy Number as the Most Positive Biomarker in Determining Which Patients are Most Likely to Benefit From gefitinib (Iressa(TM))

    Macclesfield, England, November 15 (ots/PRNewswire)

    - For Health Professional Press Only

    - For International Journalists Only - Not for US Media

    - Retrospective ISEL Study Analysis Identifies Potential Indicator of Response to Treatment With gefitinib in Advanced NSCLC patients

    Data presented today at the AACR-NCI-EORTC(x) conference provide an  insight into a potential future direction for the targeted treatment of  advanced non-small cell lung cancer (NSCLC) with the EGFR-TKI, gefitinib  (IRESSA(TM)). A retrospective analysis of tumour samples from the ISEL study  suggests that patients with a high EGFR gene copy number, as identified by  fluorescent in situ hybridisation (FISH), may be more likely to benefit from  treatment with gefitinib[1].

    Of the 370 patients with tumour samples evaluated for EGFR gene copy number, approximately one third (31%, 114 patients) were found to be FISH positive, and were therefore classifiable as having a high EGFR gene copy number[1]. Among these patients with high EGFR gene copy number, median survival appeared longer for those treated with gefitinib compared with those who received placebo (HR=0.61, 95% CI 0.36-1.04, p=0.067) with a median survival of 8.3 months vs. 4.5 months respectively[1]. For patients with low EGFR gene copy number, there was no difference between treatment groups (HR 1.16, 95% CI 0.81-1.64, p=0.4171). These new findings offer a further insight into which NSCLC tumours may respond to inhibition of the EGFR pathway, and appear consistent with findings in another placebo controlled study of an EGFR TKI in NSCLC and with several single arm studies of gefitinib in lung cancer.

    "Of the biomarkers evaluated from ISEL, high EGFR gene copy number appears to be the strongest biological predictor of a gefitinib-related effect on survival, even in patients with clinical factors associated with a poor effect," stated Fred R. Hirsch, MD, Professor of Medicine & Pathology, University of Colorado Cancer Center, United States, and lead investigator of the analysis. "What these data represent is a valuable step forward in understanding which patients suffering with this devastating, and usually fatal, disease could benefit from treatment with gefitinib."

    Further data, also presented at the conference, provide additional evidence that EGFR mutations may also be a useful indicator of response to gefitinib, a concept first reported by Lynch et al[2] and Paez et al[3] in  2004. In another analysis of the ISEL data, mutations in the EGFR tyrosine  kinase domain were found in tumours from 26 of 215 evaluable tumour samples [4]. EGFR mutations were predominantly, but not exclusively, found in tumour  samples from patients with adenocarcinomas, patients of Asian origin, females  and patients who had never smoked. EGFR mutation-positive patients treated  with gefitinib appeared to have a higher objective response rate and a  reduction in treatment failures compared with EGFR mutation-positive patients  who received placebo[4]. Gefitinib did not increase response rate or  influence treatment failure, compared with placebo in mutation-negative  patients. Due to the low overall incidence of mutations (12%), there were  insufficient data to assess the impact of mutations on survival.  Interestingly, around two thirds of EGFR mutations were found in patients who  were also positive for FISH and EGFR protein expression[4].

    Brian Holloway, IRESSA Science Director, AstraZeneca commented, "We are now making progress in evaluating potential biomarker determinants of clinical benefit with gefitinib.

    AstraZeneca has an on-going broad collaboration with leading academic institutions around the world to help identify which patients are most likely to benefit from gefitinib, and is continuing its clinical research programme in the use of the drug in other NSCLC treatment settings and other tumour types."


    1. Hirsch, FR. et al. Molecular Analysis of EGFR Gene Copy Number, EGFR Expression and Akt Activation Status in Advanced Non-small-cell Lung Cancer (aNSCLC) Treated with Gefitinib or Placebo (ISEL trial). AACR-NCI-EORTC 2005, Abs. A268.

    2. Lynch, T.J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39.

    3. Paez, J.G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676 ):1497-500.

    4. Holloway, B. et al. Epidermal growth factor (EGFR), K-Ras and B-Raf mutation status and clinical outcome to gefitinib (IRESSA) in a Phase III placebo-controlled study (ISEL) in advanced non-small-cell lung cancer (aNSCLC). AACR-NCI-EORTC 2005. Abs. A269.

    Notes to Editors:

    While the ISEL trial did not meet its primary endpoint of significantly improved survival with gefitinib in the overall population, it is important to recognise there was an increase in survival in patients of Asian origin and in patients who had never smoked.

    (x) - AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications, Philadelphia, United States.

    'IRESSA' is a trademark, the property of the AstraZeneca group of companies.

    AstraZeneca (LSE: AZN) is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

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