New Data Show Benefit of Tagrisso in Patients with EGFR-mutated Non-small Cell Lung Cancer and Central Nervous System Metastases

Phase III FLAURA trial demonstrates 52% risk reduction of CNS
disease progression or death in patients treated with Tagrisso
(osimertinib) compared to current standard-of-care EGFR-TKIs*

CAMBRIDGE, England–(BUSINESS WIRE)–AstraZeneca today presented new data from a subgroup analysis of the
Phase III FLAURA trial, which explored osimertinib as 1st-line therapy
in patients with locally advanced or metastatic epidermal growth factor
receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).
Results presented at the ESMO Asia 2017 Congress in Singapore showed
that patients with central nervous system (CNS) metastases at baseline
had a higher objective response rate with their brain metastasis and
suggest a lower risk of CNS progression when treated with osimertinib, a
third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI),
versus current standard-of-care EGFR-TKIs (erlotinib or gefitinib)
[Abstract LBA5].1

The analysis included patients with ≥1 measurable and/or non-measurable
CNS lesion present on baseline scan (as assessed by blinded independent
central review), accounting for 23% of the total FLAURA patient
population (128 of 556 patients; 61 patients enrolled in the osimertinib
arm and 67 patients in the comparator arm).1 In this
pre-specified subgroup analysis, osimertinib demonstrated a nominally
statistically significant improvement in CNS progression-free survival
(PFS) compared with current standard of care, reducing the risk of CNS
disease progression or death by more than half (hazard ratio 0.48; 95%
confidence interval [CI] 0.26-0.86; nominal p=0.014).1 In
addition, fewer patients in the osimertinib arm experienced disease
progression due to the development of new CNS lesions, compared with
patients in the comparator arm (12% vs. 30%).1 The CNS
objective response rate (a measurement of tumour shrinkage) was also
higher in patients treated with osimertinib at 66% vs. 43% for patients
in the comparator arm (odds ratio 2.5; 95% CI 1.2, 5.2; p=0.011).1

The FLAURA safety data for osimertinib were in line with those
observed in prior clinical trials.1,2 Osimertinib was
well tolerated, with less frequent Grade 3 or higher adverse events
(AEs) than with standard EGFR-TKIs (34% vs. 45%). In patients treated
with osimertinib, the most common AEs were diarrhoea (58% [2% Grade ≥3])
and dry skin (32% [<1% Grade ≥3]), and in the comparator arm group, the most common AEs were diarrhoea (57% [3% Grade ≥3]) and dermatitis acneiform (48% [5% Grade ≥3]).2

Dr. Johan Vansteenkiste, Respiratory Oncologist at the University
Hospital KU Leuven, Leuven, Belgium, said: “CNS metastases, including
brain metastases, are a common and very disabling complication of
advanced EGFR mutation-positive NSCLC. They are notoriously difficult to
treat, as existing oral therapies are often unable to effectively cross
the blood-brain barrier. The CNS efficacy results for osimertinib in the
FLAURA trial suggest improved clinical outcomes in an area of great
unmet medical need.”

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: “Osimertinib represents the
next generation of targeted therapies in EGFR mutation-positive NSCLC,
and its CNS activity has been demonstrated in the AURA3, BLOOM and
FLAURA trials. This subgroup analysis of FLAURA further supports data
presented earlier this year in demonstrating the consistent benefit of
osimertinib when used as a 1st-line therapy, irrespective of the
presence of CNS metastases at study entry.”

Full results of the FLAURA trial were published online today in the New
England Journal of Medicine
(NEJM).

*

Risk reduction was nominally statistically significant

– ENDS –

NOTES TO EDITORS

About NSCLC
Lung cancer is the leading cause of cancer
death among both men and women, accounting for about one-quarter of all
cancer deaths, more than breast, prostate and colorectal cancers
combined.3 Approximately 10-15% of patients in the US and
Europe, and 30-40% of patients in Asia have EGFR mutation-positive
(EGFRm) NSCLC.4,5,6 These patients are particularly sensitive
to treatment with currently available EGFR-TKIs, which block the
cell-signaling pathways that drive the growth of tumour cells.7
However, tumours almost always develop resistance to EGFR-TKI treatment
leading to disease progression.8 Approximately half of
patients develop resistance to approved EGFR-TKIs such as gefitinib and
erlotinib due to the resistance mutation, EGFR T790M. Osimertinib also
targets this secondary mutation that leads to disease progression.8,9
There is also a need for medicines with improved CNS efficacy, since
approximately 25% of patients with EGFR-mutated NSCLC have brain
metastases at diagnosis, increasing to approximately 40% within two
years of diagnosis.10

About Tagrisso
Tagrisso (osimertinib) is
a third-generation, irreversible EGFR-TKI designed to inhibit both
EGFR-sensitising and EGFR T790M-resistance mutations, with clinical
activity against CNS metastases.11 Osimertinib 40mg
and 80mg once-daily oral tablets have been approved in more than 60
countries, including the US, EU, Japan and China, for patients with EGFR
T790M mutation-positive advanced NSCLC. Osimertinib is also
being investigated in the adjuvant setting and in combination with other
treatments.12,13

About FLAURA
The FLAURA trial assessed the efficacy and
safety of osimertinib 80mg once daily vs. standard-of-care
EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib
[250mg orally, once daily]) in previously untreated patients with
locally advanced or metastatic EGFR-mutated NSCLC.2 The trial
was a double-blinded, randomised study, with 556 patients across 29
countries.2

About AstraZeneca in Lung Cancer
AstraZeneca is committed
to developing medicines to help every patient with lung cancer. We have
two approved medicines and a growing pipeline that targets genetic
changes in tumour cells and boosts the power of the immune response
against cancer. Our unrelenting pursuit of science aims to deliver more
breakthrough therapies with the goal of extending and improving the
lives of patients across all stages of disease and lines of therapy.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted
heritage in Oncology and offers a quickly-growing portfolio of new
medicines that has the potential to transform patients’ lives and the
Company’s future. With at least six new medicines to be launched between
2014 and 2020, and a broad pipeline of small molecules and biologics in
development, we are committed to advance New Oncology as one of
AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and
blood cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the delivery of
our strategy, as illustrated by our investment in Acerta Pharma in
haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalised
combinations, AstraZeneca has the vision to redefine cancer treatment
and one day eliminate cancer as a cause of death.

About AstraZeneca
AstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery, development and
commercialisation of prescription medicines, primarily for the treatment
of diseases in three therapy areas – Oncology, Cardiovascular &
Metabolic Diseases and Respiratory. The Company also is selectively
active in the areas of autoimmunity, neuroscience, and infection.
AstraZeneca operates in over 100 countries and its innovative medicines
are used by millions of patients worldwide.

For more information, please visit www.astrazeneca.com and
follow us on Twitter @AstraZeneca.

Intended audiences
This press release is issued from
AstraZeneca Corporate Headquarters in Cambridge, UK and is intended to
provide information about our global business. Please be aware that
information relating to the approval status and labels of approved
products may vary from country to country, and a country-specific press
release on this topic may have been issued in the countries where
AstraZeneca conducts business. Osimertinib is not yet licensed for the
1st-line treatment of EGFRm NSCLC anywhere in the world.

References

1 Vansteenkiste J, et al. CNS Response to Osimertinib
Vs. Standard-of-Care EGFR-TKI as First-Line Treatment in Patients with
EGFRm Advanced NSCLC: FLAURA. Presented at the European Society of
Medical Oncology (ESMO) Asia 2017 Congress, 17-19 November 2017,
Singapore.

2 Ramalingam S, et al. Osimertinib vs SoC EGFR-TKI as
First-Line Treatment in Patients with EGFRm Advanced NSCLC (FLAURA).
Presented at the European Society for Medical Oncology (ESMO) 2017
Congress, 8-12 September 2017, Madrid, Spain.

3 American Cancer Society. Key Statistics for Lung Cancer.
Available at https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html.
Accessed November 2017.

4 Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing
on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a
Polish, Single Institution Study and Systematic Review of European
Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.

5 Keedy VL, et al. American Society of Clinical
Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor
(EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung
Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J
Clin Oncol
. 2011:29;2121-27.

6 Ellison G, et al. EGFR Mutation Testing in Lung
Cancer: a Review of Available Methods and Their Use for Analysis of
Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.

7 Langer CJ, et al. Epidermal Growth Factor Receptor
Inhibition in Mutation-Positive Non-Small-Cell Lung Cancer: Is Afatinib
Better or Simply Newer? J Clin Oncol. 2013:31(27);3303-05.

8 Yu HA, et al. Analysis of Tumour Specimens at the
Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with
EGFR-Mutant Lung Cancer. Clin Cancer Research. 2013:19(8);2240-46.

9 Wu SG, et al. The Mechanism of Acquired Resistance
to Irreversible EGFR Tyrosine Kinase Inhibitor Afatinib in Lung
Adenocarcinoma Patients. Oncotarget. 2016:7(11);12404-13.

10 Rangachari, et al. Brain Metastases in Patients
with EGFR-Mutated or ALK-Rearranged NonSmall-Cell Lung Cancers. Lung
Cancer
. 2015;88,108–111

11 Cross DAE, et al. AZD9291, an Irreversible EGFR
TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung
Cancer. Cancer Discov. 2014:4;1046-61.

12 National Institutes of Health. AZD9291 Versus Placebo in
Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following
Complete Tumour Resection With or Without Adjuvant Chemotherapy
(ADAURA). Available at: https://www.clinicaltrials.gov/ct2/show/NCT02511106.
Accessed November 2017.

13 National Institutes of Health. AZD9291 in Combination With
Ascending Doses of Novel Therapeutics. Available at: https://clinicaltrials.gov/ct2/show/NCT02143466.
Accessed November 2017.

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