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Final Analysis of Landmark IPASS Study Confirms That IRESSA (Gefitinib) is a Valuable Option for the First-Line Treatment of Patients With Advanced NSCLC With EGFR Activating Mutations

Milan (ots/PRNewswire)

This press release has been
made available on worldwide (excluding US) press communication media
for the benefit of correspondents writing for the medical
professional press. Differing national legislation, codes of
practice, medical practice etc mean that you should contact your
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country. Not for US or Canadian journalists/publications.
Mature data from the IPASS study, presented today at the 2010
ESMO congress, showed that overall survival (OS) was similar, with no
significant difference, between IRESSA (an EGFR tyrosine kinase
inhibitor (TKI)) and carboplatin/paclitaxel (doublet chemotherapy) in
the overall population (HR=0.90, 95% CI 0.79-1.02, p=0.11, median OS
18.8 vs. 17.4 months). Neither was there a significant difference
between treatment arms for OS in the subgroups defined by EGFR
mutation status: EGFR mutation-positive patients (HR=1.00, 95% CI
0.76-1.33, median OS 21.6 vs. 21.9 months); EGFR mutation-negative
patients (HR=1.18, 95% CI 0.86-1.63, median OS 11.2 vs. 12.7 months);
and patients whose EGFR mutation status was unknown (HR=0.82, 95% CI
0.70-0.96, median OS 18.9 vs. 17.2 months).[1]
(Photo:  http://www.newscom.com/cgi-bin/prnh/20101011/412970-a )
(Photo:  http://www.newscom.com/cgi-bin/prnh/20101011/412970-b )
The mature IPASS OS data confirm that patients with EGFR
mutation-positive advanced non-small cell lung cancer (NSCLC) had
better outcomes, regardless of which treatment arm they were in,
compared to patients with EGFR mutation-negative disease. Median
survival times were around 22 months for EGFR mutation-positive
patients, but only 11-12 months for EGFR mutation-negative
patients.[1] The majority of EGFR  mutation-positive patients in
IPASS received an EGFR-TKI at some point as 64%  of those randomised
to carboplatin/paclitaxel later received an EGFR-TKI as  subsequent
therapy.
"I believe that progression-free survival is a better endpoint
than overall survival for evaluation of treatment effect in the
first-line setting," said IPASS investigator, Professor James Yang
from National Taiwan University Hospital. "However, the IPASS data
show that EGFR mutation-positive patients have better survival
outcomes than EGFR mutation-negative patients, regardless of whether
they were randomised to IRESSA or chemotherapy. Lung cancer patients
should be tested to determine their EGFR mutation status, as EGFR
mutation-positive patients benefit from treatment with IRESSA through
longer progression-free survival, improved control of their symptoms
and better quality of life, compared with doublet chemotherapy. It's
important to consider very carefully when choosing a first-line
treatment for advanced NSCLC, as many patients in clinical practice
will not receive further active treatment."
Analysis of the primary endpoint of IPASS in 2008 demonstrated
that IRESSA was superior to carboplatin/paclitaxel in terms of
progression-free survival (PFS) in the overall population (HR 0.74,
95% CI 0.65-0.85, p<0.001).[2] Further analysis of the data
demonstrated that IRESSA's PFS superiority in the overall population
was driven by the effect of IRESSA vs. carboplatin/paclitaxel in the
subgroup of EGFR mutation-positive patients.[2] In these patients,
compared with carboplatin/paclitaxel, IRESSA reduced the risk of
progression by 52% (HR=0.48, 95% CI 0.36-0.64, p<0.001) and median
progression-free survival was increased from 6.3 to 9.5 months. In
addition, IRESSA provided significant benefits in objective response
rate, quality of life and symptom improvement compared with
carboplatin/paclitaxel in EGFR mutation-positive patients.[2,3]
"IPASS is a landmark study, which changed the way the oncology
community viewed lung cancer," said Alison Armour, Medical Science
Director for AstraZeneca. "It was anticipated that the significant
IRESSA progression-free survival benefit may not translate into an
overall survival benefit, due to the large amounts of subsequent
treatment that patients could have received following disease
progression on their randomised first-line treatment. IPASS data
reinforce that there should be a move towards recognising that lung
cancer is a complex disease with distinct subtypes requiring targeted
medicines."
The IPASS data from 2008[2] formed part of the data package
leading to the current indication for IRESSA in Europe.[4] The ESMO
Clinical Practice Guidelines[5] for metastatic NSCLC state that
first-line treatment with a TKI is an option in patients with tumours
harbouring an activating EGFR mutation. IRESSA is currently indicated
in Europe for the treatment of patients with EGFR mutation-positive
advanced NSCLC.[4] Outside of Europe, IRESSA is licensed in a further
44 countries, labelled indications vary from country to country.
Editors Notes
About IPASS[2]
IRESSA Pan-ASia Study (IPASS) was a Phase III open label,
randomised, parallel-group study that assessed the efficacy, safety
and tolerability of IRESSA versus standard doublet chemotherapy
(carboplatin/paclitaxel) as first-line treatment in a clinically
selected population of 1,217 patients from Asia. The patients had
advanced NSCLC and had not received prior chemotherapy for advanced
disease. Their tumours were of adenocarcinoma histology. They had
either never smoked, or were former light smokers (ceased smoking at
least 15 years ago and <= 10 pack-years exposure).
The primary endpoint was progression-free survival (PFS: length
of time a patient lives without their cancer growing or spreading).
The secondary endpoints included overall survival, objective
response rate, quality of life and safety.
IPASS was published in The New England Journal of Medicine and
marked the first time a targeted monotherapy has demonstrated
significantly longer PFS than doublet chemotherapy in the first-line
treatment of EGFR mutation-positive advanced NSCLC.
About IRESSA (gefitinib)
Mode of Action: gefitinib is an EGFR-TKI (epidermal growth factor
receptor tyrosine kinase inhibitor), which targets and blocks the
activity of the EGFR-TK, an enzyme that regulates intracellular
signalling pathways implicated in cancer cell proliferation and
survival. Growth factor signalling has been identified as a key
driver of tumour growth and spread in a wide range of cancers.
IRESSA (250 mg) is a once-daily oral therapy.
IRESSA is approved in the EU for the treatment of patients with
locally advanced or metastatic NSCLC with activating mutation of
EGFR-TK. Outside of Europe, IRESSA is licensed in a further 44
countries - labelled indications vary from country to country.
IRESSA has a well-established, generally well-tolerated side
effect profile and is not typically associated with the cytotoxic
side-effects commonly seen with chemotherapy. The most commonly seen
side-effects of IRESSA are mild-to-moderate rash and diarrhoea.
To view an IRESSA MOA video, please click here:
http://www.egfr-mutation.com/EGFR-lung-cancer
To date, the number of patients who have taken IRESSA is over
300,000 and the maximum time a patient has remained on gefitinib
therapy is in excess of eight years.[6]
About EGFR mutation testing
Epidermal growth factor receptor (EGFR) is a protein found on the
surface of cells to which proteins or ligands such as epidermal
growth factor (EGF) bind. When EGF attaches to EGFR, it activates the
tyrosine kinase enzyme, triggering reactions that cause the cells to
grow and multiply.
The EGFR gene can have mutations that cause the EGFR to be
permanently activated, which in turn activates the tyrosine kinase
enzyme, triggering reactions that cause the cells to grow and
multiply. Those patients who have these mutations have EGFR
mutation-positive disease.
NSCLC is the more common of the two forms of lung cancer. The
other is small-cell lung cancer (SCLC), which accounts for 15% of
cases, whereas NSCLC accounts for approximately 85%.[7]
Approximately 10-15% of NSCLC patients in Europe[4,8,9] and
30-35% of NSCLC patients in Asia will have EGFR mutation-positive
NSCLC. [10,11]
EGFR mutation-positive NSCLC can be identified through biopsy
testing at the point of diagnosis. This is an additional test that
the oncologist requests along with other standard diagnostic tests
(histology testing) to identify what kind of lung cancer a patient
has. If done at the same time, this can avoid any delay in the start
of treatment.
A number of different laboratory tests are currently available
for this purpose, including DNA sequencing, Clamp (especially in
Japan) and Melt analysis. In addition, there is a mutation detection
technique called the TheraScreen EGFR29(R) (DxS).
For more information on EGFR mutation testing, please visit:
http://www.egfr-mutation.com
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical
business with a primary focus on the discovery, development and
commercialisation of prescription medicines. As a leader in
gastrointestinal, cardiovascular, neuroscience, respiratory and
inflammation, oncology and infectious disease medicines, AstraZeneca
generated global revenues of US $32.8 billion in 2009. For more
information please visit: http://www.astrazeneca.com
REFERENCES:
1. Yang C-H et al. Final overall survival (OS) results from a
phase III: randomised, open-label, first-line study of gefitinib (G)
v carboplatin/paclitaxel (C/P) in clinically selected patients with
advanced non-small cell lung cancer (NSCLC) in Asia (IPASS).
Presented at the European Society of Medical Oncology (ESMO)
Congress, 2010.
2. Mok T et al. Gefitinib or carboplatin-paclitaxel in pulmonary
adenocarcinoma. New England Journal Medication; 361: 947-957. 2009
3. Thongprasert S et al. Quality of life in a randomised Phase
III first-line study of gefitinib vs. carboplatin/paclitaxel in
clinically selected Asian patients with advanced non small cell lung
cancer (IPASS). Presented at IASLC-ESMO meeting, April 2010.
4. IRESSA summary of product characteristics (
http://www.emea.europa.eu/humandocs/Humans/EPAR/iressa/iressa.htm)
5. D'Addario G et al. Metastatic non-small-cell lung cancer: ESMO
Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Annals of Oncology; 21 Suppl 5:v116-9. 2010.
6. AstraZeneca data on file. 2010.
7. Allen J et al. Journal of the National Comprehensive Cancer
Network; 6 (3): 285-93. 2008.
8. Cortes-Funes H et al. Epidermal growth factor receptor
activating mutations in Spanish gefitinib-treated non-small-cell lung
cancer patients. Annals of Oncology; 16(7);1081-1086. 2005.
9. Rosell R et al. Screening for epidermal growth factor receptor
mutations in lung cancer. New England Journal of Medicine;
361:958-967. 2009.
10. Tokumo M et al. The relationship between epidermal growth
factor receptor mutations and clinicopathologic features in non-small
cell lung cancers. Clinical Cancer Research; 11; 1167-1173. 2005.
11. Yoshida K et al. Prospective validation for prediction of
gefitinib sensitivity by epidermal growth factor receptor gene
mutation in patients with nonsmall cell lung cancer. Journal of
Thoracic Oncology; 2(1); 22-28. 2007.

Contact:

CONTACT: For further information: Name: David Ginivan, Title: Global
PRDirector for IRESSA, Organisation: AstraZeneca,
Email:David.Ginivan@astrazeneca.com, Telephone: +44-(0)1625
516973,Mobile: +44-(0)7775 412619; Name: Jessie Prynne,Title: Account
Manager,Organisation: Edelman, Email:
Jessie.Prynne@edelman.com,Telephone:+44-(0)20-3047-2118,Mobile:
+44-(0)7834-819000

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