Predictor of Response to IRESSA(TM) (Gefitinib) Investigated in First Prospective Biomarker Study

ATLANTA, June 5 /PRNewswire/ --

-- Study Provides Further Evidence That High EGFR Gene Copy Number Correlates With Increased Response to IRESSA in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients

Data announced today at the 42nd American Society of Clinical Oncology (ASCO) Annual Meeting further advanced the understanding of the importance of biomarkers in the treatment of non-small cell lung cancer (NSCLC). Data presented from the ONCOBELL study, the first prospective biomarker study to report in NSCLC, demonstrate that response to treatment with IRESSA(TM) (gefitinib) amongst patients who had a high EGFR gene copy number, as identified by fluorescence in situ hybridization (FISH), or EGFR FISH positive, was 68%.(1) The study included patients receiving IRESSA as their first or subsequent treatment. These data provide further evidence to suggest that high EGFR gene copy number is a strong predictor of response to treatment with IRESSA for advanced NSCLC.

Of the 42 patients enrolled in the ONCOBELL trial, a phase II study designed to evaluate the effects of IRESSA in patients with advanced or metastatic NSCLC who were never smokers and/or EGFR FISH positive/phosphor-akt (pAKT) positive, 47% experienced an objective response (1 complete response; 19 partial responses).(1) However, when specifically assessing those patients who were identified as being EGFR FISH positive (n=25), 68% of patients experienced a response,(1) leading the study authors to conclude that IRESSA is a "highly effective" treatment in these patients.

Lead investigator of the ONCOBELL trial, Professor Federico Cappuzzo, MD, Ospedale Bellaria Hospital, Bologna, Italy, stated, "These data are very exciting because they suggest that we can identify, with a greater degree of certainty, those patients who may be more likely to respond to treatment with IRESSA." Professor Cappuzzo went on, "This study indicates that, by identifying this biological marker in patients prior to treatment, we can ensure they are prescribed a therapy they are likely to respond to. This should be welcome news to both clinicians and patients."

These new findings provide further support to the outcomes of an analysis of 370 tumour samples evaluated for EGFR gene copy number from the ISEL study in which approximately one third (31%, 114 patients) were found to have EGFR FISH positive tumours.(2) These EGFR FISH positive patients appeared to achieve better survival outcomes and a higher objective response rate when treated with IRESSA, compared with placebo.

Further data also presented today from an analysis of 190 patients with advanced NSCLC suggest response to platinum based chemotherapy was not associated with EGFR FISH or HER2 FISH status.(3) Although these data are investigational, in conjunction with evidence from previous studies,(4,5) they suggest that EGFR FISH positive status may be more predictive in identifying patients who are likely to benefit from treatment with EGFR-TKI therapy, such as IRESSA, as opposed to identifying those likely to benefit from chemotherapy.

Dr Nick Botwood, Worldwide Medical Director IRESSA, AstraZeneca, commented, "These data are very interesting. With the growing volume of evidence about the predictive value of a range of biomarkers, we are beginning to be able to define more clearly which biomarkers could be used to predict response to therapy. In the future, this may allow clinicians to tailor treatment to a specific patient's needs. AstraZeneca continues to evaluate the role of biomarkers in identifying which patients will respond to IRESSA in ongoing trials."

IRESSA is approved in 36 countries for the treatment of advanced NSCLC.

Notes to Editors:

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

AstraZeneca 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 $23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

For more information about AstraZeneca, please visit: www.astrazeneca.com

References

1. Cappuzzo F, et al. Clinical and biological effects of gefitinib in EGFR FISH positive/phospho-akt positive or never smoker non-small cell lung cancer (NSCLC): Preliminary results of the ONCOBELL trial. ASCO 2006, Abs. 7023.

2. 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.

3. Toschi L, et al. Tyrosine kinase inhibitors and chemotherapy target different non-small cell lung cancer (NSCLC) patient populations. ASCO 2006, Abs. 7111.

4. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). The Lancet 2005;366(9496 ):1527-37.

5. Tsao MS, et al. Erlotinib in Lung Cancer - Molecular and Clinical Predictors of Outcome. New England Journal of Medicine 2005;353:133-144.

Janet Milton-Edwards, AstraZeneca, Tel: +44-1625-515-275, Mobile: +44-7990-640-119, janet.milton-edwards@astrazeneca.com; Odette England, AstraZeneca, Mobile: +44-7743-927-226, odette.england@astrazeneca.com