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Phase III Study Data With Vandetanib (Zactima(TM)) in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Presented at American Society of Clinical Oncology

Orlando, Florida (ots/PRNewswire)

Data from the Phase III
ZODIAC(1) study in advanced non-small cell lung cancer patients, with
the investigational drug vandetanib, were presented today at the
American Society of Clinical Oncology (ASCO) meeting in Orlando.
Results show that the study met its primary endpoint, demonstrating
that the addition of vandetanib to docetaxel resulted in a
statistically significant improvement in progression-free survival
(PFS), the length of time a patient lives without their cancer
growing (hazard ratio [HR] 0.79, 97.58% CI 0.70-0.90; P<0.001. Median
PFS: 14.0 weeks vs. 17.3 weeks, favouring vandetanib). Vandetanib is
the first oral targeted therapy to show evidence of clinical benefits
when added to chemotherapy in a Phase III study in second line
advanced NSCLC(1).
To view the Multimedia News Release, please click:
http://www.prnewswire.com/mnr/astrazeneca/38570/
ZODIAC is a randomised, double-blind, placebo-controlled Phase
III study evaluating the combination of vandetanib 100mg with
docetaxel versus docetaxel alone. The study enrolled 1391 patients
previously treated with one prior anti-cancer therapy for advanced
NSCLC.
Data from ZEAL(2), a smaller Phase III study also featured on
this year's ASCO program, are supportive of ZODIAC although the
primary endpoint did not reach statistical significance in the ZEAL
study (hazard ratio [HR] 0.86, 97.58% CI 0.69-1.06; P=0.108. Median
PFS: 11.9 weeks vs. 17.6 weeks, favouring vandetanib). The
combination of vandetanib plus pemetrexed did show a positive trend
in prolongation of PFS compared with pemetrexed alone.
ZEAL is a randomised, double-blind, placebo-controlled Phase III
study evaluating vandetanib 100mg plus pemetrexed versus pemetrexed
alone. The study enrolled 534 patients previously treated with one
prior anti-cancer therapy for advanced NSCLC.
Evaluation of secondary endpoints in the ZODIAC and ZEAL studies
showed that the addition of vandetanib to chemotherapy significantly
improved objective response rate, which is a measurement of tumour
shrinkage (ZODIAC: 17% vs. 10%, P<0.001; ZEAL: 19.1% vs. 7.9%,
P<0.001), the studies also showed that adding vandetanib to
chemotherapy resulted in a significantly longer time to deterioration
of disease related symptoms (ZODIAC: HR 0.78, P=0.002, FACT-L Lung
Cancer Subscale; ZEAL: HR 0.61, P=0.004, Lung Cancer Symptom Scale).
Overall survival in both studies showed a positive trend, although
they did not reach statistical significance (ZODIAC Study: HR 0.91,
97.52% CI 0.78-1.07: P=0.196; ZEAL Study: HR 0.86, 97.54% CI
0.65-1.13; p=0.219).
The observed safety profile in both studies was consistent with
previous studies with vandetanib in NSCLC. The most common adverse
events associated with vandetanib included rash, diarrhoea and
hypertension (ZEAL); rash, diarrhoea and neutropenia (low white blood
cell count) (ZODIAC). Incidence of protocol-defined QTc prolongation
was <2.0 percent in both studies and was not associated with
symptoms.
"There are more deaths from lung cancer alone than from breast,
colon, and prostate cancers combined - and it's extremely difficult
to treat," said Professor Roy Herbst, M.D., Ph.D., The University of
Texas M. D. Anderson Cancer Center, Texas, Principal Investigator on
the ZODIAC study. "The ZODIAC study showed adding vandetanib to
chemotherapy improved progression-free survival, in patients who have
few, if any options for treatment."
Results from a third Phase III study, ZEST(3), were also
presented at  This year's ASCO. While the primary objective of
demonstrating a  statistically significant prolongation of PFS for
vandetanib was not met in  this study, in a pre-planned
non-inferiority analysis, vandetanib was shown  to have similar
efficacy to erlotinib for PFS and OS (PFS: hazard ratio [HR]  0.98,
95.22% CI 0.87-1.10; P=0.721; OS: HR 1.01, 95.08% CI 0.89-1.16;
P=0.830). Objective response rate and symptom control were also
similar for  both treatments (ORR: both 12%; symptoms: pain, HR 0.96,
P=0.583; dyspnea, HR  1.08, P=0.333; cough, HR 0.94, P=0.403).
The ZEST study was a randomised, double-blind, Phase III study
evaluating the efficacy of vandetanib 300mg versus erlotinib 150mg.
The study enrolled 1240 patients with locally advanced or metastatic
NSCLC after failure of at least one prior anti-cancer therapy.
The most common adverse events observed in the ZEST study were
rash, diarrhoea and hypertension. Incidence of protocol-defined QTc
prolongation was 5.1 percent in the vandetanib arm.
AstraZeneca plans to submit a regulatory submission for the use
of vandetanib 100mg in combination with chemotherapy for patients
with advanced NSCLC in the first half of 2009.
Evaluation of vandetanib is ongoing, as monotherapy or in
combination with other anti-cancer therapies in a range of tumour
types, including thyroid cancer.
Results from the ZEPHYR (300mg monotherapy study in EGFR failures
in advanced NSCLC, Phase III) and ZETA (300 mg monotherapy in
advanced medullary thyroid cancer, Phase III) studies will be
available during the second half of 2009.
ZACTIMA(TM) is a trademark of the AstraZeneca group of companies.
Notes To Editors
About vandetanib
Vandetanib has a unique profile that fights cancer through two
clinically proven mechanisms - by blocking the development of tumour
blood supply (anti-angiogenesis or anti-VEGFR), and by blocking the
growth and survival of the tumour itself (anti-EGFR). Vandetanib also
inhibits RET-tyrosine kinase activity, an important growth driver in
certain types of thyroid cancer.
About the Phase III studies in NSCLC
ZODIAC (ZACTIMA in cOmbination with Docetaxel In non-smAll cell
lung Cancer) is a Phase III randomised, double-blind,
placebo-controlled study evaluating the combination of vandetanib
100mg once daily plus docetaxel versus docetaxel alone in patients
with locally advanced or metastatic NSCLC, treated with one prior
anti-cancer therapy. It enrolled 1391 patients at 250 centres
throughout Europe, North America, South America and Asia Pacific.
ZEAL (ZACTIMA Efficacy with Alimta in Lung cancer) is a
randomised, double-blind, placebo-controlled Phase III study
evaluating the combination of vandetanib 100mg with pemetrexed versus
pemetrexed alone in patients with locally advanced or metastatic
NSCLC, treated with one prior anti-cancer therapy. It enrolled 534
patients at 160 centres across 23 countries.
ZEST (ZACTIMA Efficacy Study versus Tarceva) is a Phase III
randomised, double-blind, multi-centre study to assess the efficacy
of vandetanib 300mg versus erlotinib in patients with locally
advanced or metastatic NSCLC after failure of at least one prior
anti-cancer therapy. It enrolled 1240 patients at 171 centres across
22 countries.
ZEPHYR (ZACTIMA Efficacy trial for NSCLC Patients with HistorY of
EGFR-TKI and chemo-Resistance) is a Phase III, randomised,
double-blind, parallel-group, multi-centre study evaluating the
efficacy of ZACTIMA 300mg plus best supportive care versus best
supportive care in patients with locally advanced or metastatic
(stage IIIB-IV) NSCLC after prior therapy with an EGFR inhibitor. The
study is running in approximately 170 centres across 23 countries.
ZETA (Zactima Efficacy in Thyroid Cancer Assessment) is a phase
III, randomized, double-blind, placebo-controlled, multi-centre
study, evaluating once-daily ZACTIMA 300mg as a monotherapy in
advanced medullary thyroid cancer.
    About lung cancer
    - Over 1.35 million new cases of lung cancer are diagnosed
      every year and nearly 1.2 million people die as a result of this
      devastating disease - more than breast, colon and prostate cancer
      combined(4).
    - Non-small cell lung cancer accounts for around 85% of all ung
      cancers(5).
    - If lung cancer is detected at early stages, before it has
      spread to other organs or lymph nodes, around half of patients can
      survive for five years or more. However, few lung cancers are found at
      this early stage and it is normally diagnosed at the advanced stage,
      when five year survival falls to approximately 15%(6).
About AstraZeneca
AstraZeneca is a major international healthcare business engaged
in the research, development, manufacturing and marketing of
meaningful prescription medicines and supplier for healthcare
services. AstraZeneca is one of the world's leading pharmaceutical
companies with healthcare sales of US$ 31.6 billion and is a leader
in gastrointestinal, cardiovascular, neuroscience, respiratory,
oncology and infectious disease medicines. For more information about
AstraZeneca, please visit: http://www.astrazeneca.com
The statements contained herein include forward-looking
statements. Although we believe our expectations are based on
reasonable assumptions, any forward-looking statements, by their very
nature, involve risks and uncertainties and may be influenced by
factors that could cause actual outcomes and results to be materially
different from those predicted. The forward-looking statements
reflect knowledge and information available at the date of the
preparation of this press release and the Company undertakes no
obligation to update these forward-looking statements. Important
factors that could cause actual results to differ materially from
those contained in forward-looking statements, certain of which are
beyond our control, include, among other things, those risk factors
identified in the Company's Annual Report/Form 20-F for 2008. Nothing
contained herein should be construed as a profit forecast.
Reference List
(1) Herbst, R. et al. Vandetanib plus docetaxel vs docetaxel as
2nd-line treatment for patients with advanced non-small-cell lung
cancer  (NSCLC): a randomized, double-blind phase III trial (ZODIAC).
ABS 31495.  ASCO. 2009.
(2) De Boer, R. et al. Vandetanib plus pemetrexed vs pemetrexed
as  2nd-line therapy in patients with advanced non-small-cell lung
cancer  (NSCLC): a randomized, double-blind phase III trial (ZEAL).
ABS 31867, ASCO. 2009.
(3) Natale, R. et al. Vandetanib versus erlotinib in patients
with advanced non-small-cell lung cancer (NSCLC) after failure of at
least 1  prior cytotoxic chemotherapy: a randomized, double-blind
phase III trial (ZEST). ABS 31610. ASCO. 2009.
(4) Ferlay, J. et al. GLOBOCAN 2002: Cancer Incidence, Mortality
and  Prevalence Worldwide. IARC CancerBase No. 5. version 2.0. Lyon:
IARC Press,  2004.
(5) Ginsberg RJ. et al. Cancer: Principles and Practices of
Oncology.  5th ed; 858-911. 1997. 6th ed. 925-983. 2001.
(6) Bepler G. Lung cancer epidemiology and genetics. J Thorac
Imaging  1999; 14(4):228-234.

Contact:

Full results from the Phase III studies will be presented at a media
briefing on Saturday 30th May. For more details, please contact Emma
Overington on emma.overington@porternovelli.co.uk or
+44-7971-769-239. Contacts: Janet Milton-Edwards, AstraZeneca, Tel :
+44-1625-515275, Mob : +44-7990-640-119,
Janet.milton-edwards@astrazeneca.com. Emily Denney, AstraZeneca US,
Tel : +1-302-885-3451, Mob : +1-302-897-4953,
Emily.Denney@astrazeneca.com

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