a1176a
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 May 2021
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 approved in the
EU for the adjuvant treatment
of patients with early-stage EGFR-mutated lung cancer
28 May 2021 07:00 BST
Tagrisso approved in the EU for the adjuvant
treatment
of patients with early-stage EGFR-mutated lung
cancer
Approval based on unprecedented results from the ADAURA Phase III
trial
where Tagrisso reduced the risk of disease recurrence or death by
80%
AstraZeneca's Tagrisso (osimertinib) has been approved in the
European Union (EU) for the adjuvant treatment of adult patients
with early-stage (IB, II and IIIA) epidermal growth factor
receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after
complete tumour resection with curative
intent. Tagrisso is indicated for EGFRm patients whose
tumours have exon 19 deletions or exon 21 (L858R)
mutations.
The approval by the European Commission was based on positive
results from the ADAURA Phase III trial in
which Tagrisso demonstrated a statistically significant and
clinically meaningful improvement in disease-free survival (DFS) in
the primary analysis population of patients with Stage II and IIIA
EGFRm NSCLC. The trial also showed a statistically significant and
clinically meaningful improvement in DFS
for Tagrisso in the overall trial population, a key
secondary endpoint.
While up to 30% of all patients with NSCLC may be diagnosed early
enough to have surgery with curative intent, recurrence is still
common in early-stage disease. Historically, nearly half of
patients diagnosed in Stage IB, and over three quarters of patients
diagnosed in Stage IIIA, have experienced disease recurrence within
five years.1-3 About
a fifth of the world's lung cancer patients are in the EU and among
those with NSCLC, approximately 15% have tumours with an EGFR
mutation.4-6
Margarita Majem, MD, PhD, Department of Medical Oncology, Hospital
de la Santa Creu i Sant Pau, Spain, said: "In the early stages
of lung cancer, where tumour resection is possible but recurrence
is far too common, adjuvant Tagrisso has shown an unprecedented disease-free
survival benefit for patients with EGFR mutations. I expect this
approval will change clinical practice in the EU, as it heightens
the critical importance of EGFR mutation testing across all stages
of lung cancer to ensure as many patients as possible can benefit
from targeted medicines like Tagrisso."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "We know the earlier a patient's cancer is detected and
treated, the greater chance they may have of being cured, which is
why this approval is significant. For the first time, patients in
the EU with EGFR-mutated lung cancer have a targeted,
biomarker-driven treatment option available in the early stages of
their disease that can help them live cancer-free
longer."
In the ADAURA trial, adjuvant treatment
with Tagrisso reduced the risk of disease recurrence or
death by 83% in patients with Stage II and IIIA
disease (hazard ratio [HR] 0.17; 99.06% confidence interval
[CI] 0.11-0.26; p<0.001) and by 80% in the overall trial
population of patients with Stage IB-IIIA disease (HR 0.20; 99.12%
CI 0.14-0.30; p<0.001).
Consistent DFS results were seen regardless of prior adjuvant
chemotherapy use and across all prespecified subgroups. The safety
and tolerability of Tagrisso in this trial was consistent with
previous trials in the metastatic setting. The ADAURA results
were published in The
New England Journal of Medicine.
Tagrisso is now approved
to treat early-stage lung cancer in more than fifty countries,
including in the
US and China,
and additional global regulatory reviews are
ongoing. Tagrisso is also approved for the 1st-line treatment
of patients with locally advanced or metastatic EGFRm NSCLC and for
the treatment of locally advanced or metastatic EGFR T790M
mutation-positive NSCLC in the EU, the US, Japan, China and many
other countries.
Lung cancer
Lung cancer is the leading cause of cancer death among men and
women, accounting for about one-fifth of all cancer
deaths.4 Lung
cancer is broadly split into NSCLC and small cell lung cancer, with
80-85% classified as NSCLC.7 The
majority of NSCLC patients are diagnosed with advanced disease
while approximately 25-30% present with
resectable disease at diagnosis.1-2 Early-stage
lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.8-9
For patients with resectable tumours, the majority of patients
eventually develop recurrence despite complete tumour resection and
adjuvant chemotherapy.3
Approximately 10-15% of NSCLC patients in the US and Europe, and
30-40% of patients in Asia have EGFRm NSCLC.10-12 These
patients are particularly sensitive to treatment with an
EGFR-tyrosine kinase inhibitor (TKI) which blocks the
cell-signalling pathways that drive the growth of tumour
cells.13
ADAURA
ADAURA is a randomised, double-blind, global, placebo-controlled
Phase III trial in the adjuvant treatment of 682 patients with
Stage IB, II and IIIA EGFRm NSCLC following complete tumour
resection and adjuvant chemotherapy as indicated. Patients were
treated with Tagrisso 80mg once-daily oral tablets or placebo for
three years or until disease recurrence.
The trial enrolled patients in more than 200 centres across more
than 20 countries, including the US, in Europe, South America, Asia
and the Middle East. The primary endpoint was DFS in Stage II and
IIIA patients and a key secondary endpoint was DFS in Stage IB, II
and IIIA patients.
The data readout was originally anticipated in 2022. In April 2020,
an Independent Data Monitoring Committee recommended for the trial
to be unblinded two years early based on a determination of
overwhelming efficacy. Treating physicians and patients continue to
participate and remain blinded to treatment. The trial will
continue to assess overall survival.
Tagrisso
Tagrisso (osimertinib) is
a third-generation, irreversible EGFR TKI with clinical activity
against central nervous system metastases. Tagrisso (40mg and 80mg once-daily oral
tablets) has been used to treat more than 250,000 patients
across indications worldwide and AstraZeneca continues to
explore Tagrisso as a treatment for patients across multiple
stages of EGFRm NSCLC.
In Phase III trials, Tagrisso is being tested in the neoadjuvant
resectable setting (NeoADAURA), in the Stage III locally advanced
unresectable setting (LAURA) and, in combination with chemotherapy,
in the Stage III locally advanced or Stage IV metastatic settings
(FLAURA2). AstraZeneca is also researching ways to address tumour
mechanisms of resistance through the SAVANNAH and ORCHARD Phase II
trials, which test Tagrisso given concomitantly with savolitinib, an
oral, potent and highly selective MET TKI, as well as other
potential new medicines.
AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to
cure through the detection and treatment of early-stage disease,
while also pushing the boundaries of science to improve outcomes in
the resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit
most.
The Company's comprehensive portfolio includes leading lung cancer
medicines and the next wave of innovations
including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and
tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab
deruxtecan in collaboration with Daiichi Sankyo; savolitinib in
collaboration with HUTCHMED; as well as a pipeline of potential new
medicines and combinations across diverse mechanisms of
action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a
global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer including and
beyond treatment.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines in
Oncology and BioPharmaceuticals, including Cardiovascular, Renal
& Metabolism, and Respiratory & Immunology. Based in
Cambridge, UK, AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Arch Pathol Lab
Med. 2013;137:1191-1198.
2. Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable
Non-Small Cell Lung Cancer: Where is it
Going? Ann Oncol. 2010;21:vii196-vii198.
3. Pignon J, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin
Oncol. 2008;26:3552-3559.
4. World Health Organization. International Agency for Research on
Cancer. Lung Fact Sheet. Available at
https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed May 2021.
5. World Health Organization. International Agency for Research on
Cancer. Globocan United Kingdom Fact Sheet 2020. Available at
https://gco.iarc.fr/today/data/factsheets/populations/826-united-kingdom-fact-sheets.pdf.
Accessed May 2021.
6. Midha A, et al. EGFR mutation incidence in non-small cell
lung cancer of adenocarcinoma histology: a systematic review and
global map by ethnicity (mutMapII). Am J Cancer
Res. 2015;5(9):2892-2911.
7. LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed May 2021.
8. Sethi S, et al. Incidental Nodule Management - Should There
Be a Formal Process?. J Thorac
Dis.
2016:8;S494-S497.
9. LUNGevity Foundation. Screening and Early Detection. Available
at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection.
Accessed May 2021.
10. 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.
11. Keedy V.L., 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.
12. 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.
13. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes
T790M-Mediated Resistance to EGFR Inhibitors in Lung
Cancer. Cancer
Discov.
2014;4(9):1046-1061.
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:
28 May
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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