FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of September
2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tagrisso is the
only 1st-line treatment for EGFR-mutated non-small cell lung cancer
to deliver a median overall survival of more than three
years
30 September 2019 07:00 BST
Tagrisso is the only 1st-line treatment for
EGFR-mutated non-small cell lung cancer to deliver a median overall
survival of more than three years
28% of patients in the global FLAURA trial were still receiving
Tagrisso at
three years vs. 9% on either gefitinib or
erlotinib
Tagrisso showed a 52% reduction in risk of central nervous
system
disease progression or death
AstraZeneca today announced overall survival (OS) results from the
Phase III FLAURA trial of Tagrisso(osimertinib) in the 1st-line treatment of adult
patients with locally advanced or metastatic epidermal growth
factor receptor (EGFR)-mutated non-small cell lung cancer
(NSCLC).
Results showed a statistically significant and
clinically meaningful improvement in OS, a key secondary endpoint
for Tagrisso versus gefitinib or erlotinib, both of which
were previous standard-of-care (SoC) treatments in this setting (HR
0.799 [95% CI, 0.641-0.997], p=0.0462).
Tagrisso delivered a median OS of 38.6 months versus
31.8 months for the comparator arm. At three years, 28% of patients
in the Tagrisso arm and 9% of patients in the comparator arm
remained on 1st-line study treatment. Tagrisso also showed a statistically significant and
clinically meaningful 52% reduction in the risk of central nervous
system (CNS) disease progression, increasing the time patients with
CNS metastases lived without CNS disease progression or death (HR
0.48 [95% CI, 0.26-0.86], p=0.014).1
The
results were presented at the Presidential Symposium of the
ESMO (European Society for Medical Oncology) 2019 Congress in
Barcelona, Spain (Abstract #LBA5_PR).
José Baselga, Executive Vice President, Oncology R&D said:
"Tagrisso has set a new benchmark in EGFR-mutated
non-small cell lung cancer by demonstrating a median overall
survival of more than three years. We have not before seen
survival benefits of this magnitude in any global Phase III
trial with any such therapy. The ground-breaking
data reaffirm the benefit of using Tagrisso first and further support its use as the
1st-line standard of care in this setting."
Dr Suresh S. Ramalingam, Principal Investigator of the FLAURA trial
from Winship Cancer Institute of Emory University, Atlanta, US,
said: "The results of the FLAURA trial provide further evidence to
support the role of osimertinib as the preferred 1st-line therapy
option for patients with EGFR-mutated non-small cell lung cancer.
It is highly noteworthy that 28% of patients are still being
treated with 1st-line osimertinib at three years versus 9% on
either gefitinib or erlotinib."
Summary of FLAURA results
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Tagrisso
(n=279)
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EGFR-tyrosine kinase inhibitors (TKI)
(gefitinib or erlotinib)
(n=277)
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Progression-free survival (PFS)
(primary endpoint)i
|
|
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Median in months
(95% CI)
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18.9
(15.2, 21.4)
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10.2 months
(9.6, 11.1)
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Hazard ratio
(95% CI)
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0.46
(0.37, 0.57)
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p-value
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p < 0.0001
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OS (secondary
endpoint)i
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Hazard ratio
(95% CI)
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0.799
(0.641-0.997)
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p-value
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p = 0.0462ii
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Median in months
(95% CI)
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38.6
(34.5-41.8)
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31.8
(26.6-36.0)
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Survival at 12 months
(95% CI)
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89.1%
(84.8-92.2)
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82.5%
(77.4-86.6)
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|
Survival at 24 months
(95% CI)
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74.2%
(68.6-79.0)
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58.9%
(52.7-64.6)
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Survival at 36 months
(95% CI)
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53.7%
(47.5-59.5)
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44.1%
(38.0-50.1)
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CNS PFS (secondary
endpoint)i,1
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|
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Hazard ratio
(95% CI)
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0.48
(0.26-0.86)
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p-value
|
p = 0.014
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|
Median in months
(95% CI)
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Not reached
(16.5-NC)iii
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13.9
(8.3-NC)iii
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Time to first subsequent therapy or
death (TFST) (exploratory endpoint)i
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|
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Hazard ratio
(95% CI)
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0.48
(0.39-0.58)
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Number (%) of patients with events
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69.5%
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87.4%
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Median in months
(95% CI)
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25.5
(22.0, 29.1)
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13.7
(12.3, 15.7)
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Time to second subsequent therapy or
death (TSST) (exploratory endpoint)i
|
|
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Hazard ratio
(95% CI)
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0.69
(0.56-0.84)
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Number (%) of patients with events
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64.5%
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73.3%
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Median in months
(95% CI)
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31.1
(28.8, 35.9)
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23.4
(20.0, 25.6)
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Patients remaining on initial study treatment
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12 months
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69.5%
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47.3%
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24 months
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42.3%
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16.2%
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36 months
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28.0%
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9.4%
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I The data cut-off date
was 25 June 2019 (OS, TFST, TSST) and 12 June 2017 (PFS, CNS
PFS)
ii Criteria for
statistical significance at the final analysis of OS was a p-value
of less than 0.0495 (determined by O'Brien- Fleming
approach)
iii NC=Not
Calculable
In the FLAURA trial, the safety and tolerability
of Tagrisso was consistent with its established
profile. Tagrisso was generally well tolerated, with Grade 3
or higher adverse events (AEs) occurring in 42% of patients
taking Tagrisso versus 47% in the comparator arm. The most
common AEs in patients treated with Tagrisso were diarrhoea (60%), rash (59%), nail
toxicity (39%), dry skin (38%), stomatitis (29%), fatigue (21%) and
decreased appetite (20%). Despite almost twice the length of
therapy, fewer patients experienced a grade 3 or higher AE (42% vs.
47%) or discontinued due to AEs (15% vs. 18%).
The FLAURA trial met its primary
endpoint in July 2017,
showing a statistically significant and clinically meaningful
improvement in PFS, increasing the time patients lived without
disease progression or death from any cause.
Tagrisso is currently
approved in 78 countries, including the US, Japan, China and the
EU, for 1st-line EGFR-mutated (EGFRm) metastatic
NSCLC.
About lung cancer
Lung cancer is the leading cause of cancer death among both men and
women, accounting for about one-fifth of all cancer deaths, more
than breast, prostate and colorectal cancers
combined.2 Lung
cancer is broadly split into NSCLC and small cell lung cancer
(SCLC), with 80-85% classified as NSCLC.3Approximately
10-15% of NSCLC patients in the US and Europe, and 30-40% of
patients in Asia have EGFRm NSCLC.4-6 These
patients are particularly sensitive to treatment with EGFR-TKIs
which block the cell-signalling pathways that drive the growth of
tumour cells. Approximately 25% of patients with EGFRm NSCLC have
brain metastases at diagnosis, increasing to approximately 40%
within two years of diagnosis.7 The
presence of brain metastases often reduces median survival to less
than eight months.8
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. Tagrisso40mg and 80mg once-daily oral tablets have now
received approval in more than 75 countries, including the US,
Japan, China and the EU, for 1st-line EGFRm advanced NSCLC, and in
more than 85 countries, including the US, Japan, China and the EU,
for 2nd-line use in patients with EGFR T790M mutation-positive
advanced NSCLC. Tagrisso is also being developed in the adjuvant
setting (ADAURA trial), in the locally-advanced unresectable
setting (LAURA), in combination with chemotherapy (FLAURA2) in the
metastatic setting, and with potential new medicines to address
resistance to EGFR-TKIs (SAVANNAH, ORCHARD).
About FLAURA
The FLAURA trial assessed the efficacy and safety
of Tagrisso 80mg orally once daily versus comparator
EGFR-TKIs (either gefitinib [250mg orally, once daily] or erlotinib
[150mg orally, once daily]) in previously-untreated patients with
locally-advanced or metastatic EGFRm NSCLC. The trial was
double-blinded and randomised, with 556 patients across 29
countries.
About AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential
new medicines in late-stage clinical development for the treatment
of different forms of lung cancer spanning several stages of
disease, lines of therapy and modes of action. We aim to address
the unmet needs of patients with EGFR-mutated tumours as a genetic
driver of disease, which occur in 10-15% of NSCLC patients in the
US and EU and 30-40% of NSCLC patients in Asia, with our approved
medicines Iressa (gefitinib) and Tagrisso, and ongoing Phase III trials ADAURA, LAURA
and FLAURA2 as well as the Phase II combination trials SAVANNAH and
ORCHARD.4-6
Our extensive late-stage Immuno-Oncology programme focuses on lung
cancer patients without a targetable genetic mutation which
represents approximately three-quarters of all patients with lung
cancer.9 Imfinzi (durvalumab),
an anti-PDL1 antibody, is in development for patients with advanced
disease (Phase III trials POSEIDON, PEARL, and CASPIAN) and for
patients in earlier stages of disease including
potentially-curative settings (Phase III trials AEGEAN, PACIFIC-2,
ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5) both as
monotherapy and in combination with tremelimumab and/or
chemotherapy.
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, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
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, Renal and
Metabolism (CVRM), and Respiratory. AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and
follow us on Twitter @AstraZeneca.
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Media Relations
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Gonzalo
Viña
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+44 203 749 5916
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Rob
Skelding
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Oncology
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+44 203 749 5821
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Rebecca
Einhorn
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Oncology
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+1 301 518 4122
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Matt
Kent
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BioPharmaceuticals
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+44 203 749 5906
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Jennifer
Hursit
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Other
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+44 203 749 5762
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Christina
Malmberg Hägerstrand
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Sweden
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+46 8 552 53 106
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Michele
Meixell
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US
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+1 302 885 2677
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Investor Relations
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Thomas
Kudsk Larsen
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+44 203 749 5712
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Henry
Wheeler
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Oncology
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+44 203 749 5797
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Christer
Gruvris
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BioPharmaceuticals (CV, metabolism)
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+44 203 749 5711
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Nick
Stone
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BioPharmaceuticals (respiratory, renal)
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+44 203 749 5716
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Josie
Afolabi
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Other medicines
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+44 203 749 5631
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Craig
Marks
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Finance, fixed income
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+44 7881 615 764
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Jennifer
Kretzmann
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Corporate access, retail investors
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+44 203 749 5824
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US
toll-free
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+1 866 381 72 77
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References
1. Vansteenkiste J, et al. CNS Response to Osimertinib vs Standard
of Care (SoC) EGFR-TKI as First-line Therapy in Patients (pts) with
EGFR-TKI Sensitising Mutation (EGFRm)-positive Advanced Non-Small
Cell Lung Cancer (NSCLC): Data from the FLAURA
Study. Annals of
Oncology. 2017:28(10);189
[Accessed September 2019].
2. World Health Organization. International Agency for Research on
Cancer. Globocan Worldwide Fact Sheet 2018. Available
at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx [Accessed
September 2019].
3. LUNGevity Foundation. Types of Lung Cancer. Available
at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer [Accessed
September 2019].
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 [Accessed
September 2019].
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
[Accessed September 2019].
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
[Accessed September 2019].
7. Rangachari, et al. Brain Metastases in Patients with
EGFR-Mutated or ALK-Rearranged Non-Small-Cell Lung
Cancers. Lung Cancer. 2015;88,108-111 [Accessed September
2019].
8. Ali A, et al. Survival of Patients with Non-small-cell Lung
Cancer After a Diagnosis of Brain
Metastases. Curr Oncol. 2013;20(4):e300-e306 [Accessed September
2019].
9. Pakkala, S, et al. Personalized therapy for lung cancer:
striking a moving target. JCI Insight. 2018;3(15):e120858.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
30 September
2019
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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