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

Atlanta (ots/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.

Originaltext: AstraZeneca
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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