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

By Astrazeneca, PRNE
Sunday, October 10, 2010

MILAN, October 11, 2010 - This press release has been made available on worldwide (excluding US)
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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: )

(Photo: )

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

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:

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:

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:


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 (

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.


For further information: Name: David Ginivan, Title: Global PR Director for IRESSA, Organisation: AstraZeneca, Email: David.Ginivan at, Telephone: +44-(0)1625 516973,
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