a5021z
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 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tagrisso reduced the risk
of disease recurrence in the brain by 82%
in the adjuvant treatment of early-stage EGFR-mutated lung
cancer
19 September 2020 17:30 BST
Tagrisso reduced
the risk of disease recurrence in the brain by
82%
in the adjuvant treatment of early-stage EGFR-mutated lung
cancer
ADAURA Phase III trial data at ESMO reinforce the proven
clinical
activity of Tagrisso in treating central nervous system
metastases
Results from a prespecified exploratory analysis of the positive
ADAURA Phase III trial showed
AstraZeneca's Tagrisso (osimertinib)
demonstrated a clinically meaningful improvement in central nervous
system (CNS) disease-free survival (DFS) in the adjuvant treatment
of patients with early-stage (IB, II and IIIA) epidermal
growth factor receptor-mutated (EGFRm) non-small cell lung cancer
(NSCLC), after complete tumour resection.
While up to 30% of all patients with NSCLC may be diagnosed early
enough to have potentially curative surgery, disease recurrence is
still common in early-stage disease.1-3 CNS
recurrence, when cancer spreads to the brain, is a frequent
complication of EGFRm NSCLC and these patients have an
especially poor prognosis.4-5
Results were presented on 19 September 2020 during the Presidential
Symposium of the European Society for Medical Oncology (ESMO)
Virtual Congress 2020 (abstract #LBA1) and simultaneously published
with the primary results in The
New England Journal of Medicine.
This analysis showed that fewer patients treated
with Tagrisso in the adjuvant setting had recurrence
events or deaths compared to placebo (11% versus 46%). Among
patients whose cancer recurred, 38% of those treated
with Tagrisso had a metastatic recurrence compared to 61%
of patients on placebo. Tagrisso showed an 82% reduction in the risk of CNS
recurrence or death (based on a hazard ratio [HR] of 0.18; 95%
confidence interval [CI] 0.10-0.33; p<0.0001). Median CNS DFS
was not yet reached in either arm.
In a post-hoc analysis, the estimated probability of observing
disease recurrence in the brain at 18 months for patients treated
with Tagrisso was less than 1% versus 9% for placebo among
patients who had not experienced another type of recurrence. On the
primary endpoint of DFS in patients with Stage II and IIIA
disease, Tagrisso in the adjuvant setting reduced the risk of
disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23;
p<0.0001).
Masahiro Tsuboi, MD, PhD, director of the Department of Thoracic
Surgery and Oncology, National Cancer Center Hospital East in
Japan, and a principal investigator in the ADAURA Phase III trial,
said: "It's time to change the notion that treatment for
early-stage EGFR-mutated lung cancer ends after surgery, since
recurrence rates are still very high even after adjuvant
chemotherapy. These new data showing low rates of recurrence,
particularly in the brain, combined with the remarkable
disease-free survival benefit, clearly demonstrate
that Tagrisso provides patients with more time living
cancer-free."
José Baselga, Executive Vice President, Oncology R&D,
said: "Once lung cancer has spread to the brain, outcomes are
typically devastating for patients. We are now
seeing Tagrisso expanding on its proven efficacy in treating
progression in the brain in the metastatic setting as a result of
its ability to cross the blood-brain barrier. The striking new data
show that Tagrisso prevents the development of brain metastases
in patients with early disease and reinforce that this medicine is
truly transformative for patients with EGFR-mutated lung
cancer. Tagrisso should become the standard of care in the
adjuvant setting, just as it is for patients with metastatic
disease around the world."
Summary of exploratory results on CNS recurrence in the ADAURA
Phase III trial
|
Tagrisson=339
|
Placebon=343
|
CNS DFS
|
|
HR
(95% CI)
|
0.18
(0.10-0.33);
|
p-value
|
p<0.0001
|
CNS DFS events, patients (%):
|
6
(2%)
|
39
(11%)
|
CNS
recurrence
|
4
(1%)
|
33
(10%)
|
Deathi
|
2
(1%)
|
6
(2%)
|
DFS events, patients (%):
|
37
(11%)
|
159
(46%)
|
Type
of disease recurrence
|
n=37
|
n=157
|
Local/regional
only
|
23
(62%)
|
61
(39%)
|
Distant
|
14
(38%)
|
96
(61%)
|
Deathii
|
0
|
2
(1%)
|
i.
Death in absence of CNS disease recurrence, or death within two
visits of baseline where the patient has no evaluable assessments
or no baseline data.
ii.
Death in the absence of disease recurrence (any site), or death
within two visits of baseline where the patient has no evaluable
assessments or no baseline data.
The safety and tolerability of Tagrisso in this trial was consistent with
previous trials in the metastatic EGFRm NSCLC setting. Adverse
events at Grade 3 or higher from all causes occurred in 10% of
patients in the Tagrisso arm versus 3% in the placebo arm as assessed
by investigators.
Tagrisso is not currently
approved in the adjuvant setting in any country. Tagrisso received Breakthrough Therapy Designation
in July
2020 for the adjuvant treatment of patients with
early-stage EGFRm NSCLC after complete tumour resection with
curative intent. Tagrisso is 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 US, Japan, China, the EU and many
other countries around the world.
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.6 Lung
cancer is broadly split into NSCLC and small cell lung cancer, with
80-85% classified as NSCLC.7 The
majority of all NSCLC patients are diagnosed with advanced disease
while approximately 25-30% present with resectable disease at
diagnosis.1-3
For those with resectable tumours, the majority of patients
eventually develop recurrence despite complete tumour resection and
adjuvant chemotherapy.8 Early-stage
lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.9-10
Approximately 10-15% of NSCLC patients in the US and Europe, and
30-40% of patients in Asia have EGFRm NSCLC.11-13 These
patients are particularly sensitive to treatment with EGFR-tyrosine
kinase inhibitors (TKIs) which block the cell-signalling pathways
that drive the growth of tumour cells.14
ADAURA
ADAURA is a randomised, double-blinded, global, placebo-controlled
Phase III trial in the adjuvant treatment of 682 patients with
Stage IB, II, 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 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 is DFS in Stage II and IIIA
patients and a key secondary endpoint is DFS in Stage IB, II and
IIIA patients. The data readout was originally anticipated in 2022.
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 have
received approval in the US, Japan, China, the EU and many
countries around the world for 1st-line EGFRm advanced NSCLC and
EGFR T790M mutation-positive advanced NSCLC.
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential
new medicines in late-stage development for the treatment of
different forms of lung cancer spanning different histologies,
several stages of disease, lines of therapy and modes of
action.
AstraZeneca aims to address the unmet needs of patients with EGFRm
tumours as a genetic driver of disease with the approved
medicines Iressa (gefitinib) and Tagrisso and its ongoing Phase III trials LAURA,
NeoADAURA and FLAURA2.
AstraZeneca is committed to addressing tumour mechanisms of
resistance through the ongoing Phase II trials SAVANNAH and
ORCHARD, which test Tagrisso in combination with savolitinib, a selective
inhibitor of c-MET receptor tyrosine kinase, along with other
potential new medicines.
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 seven
new medicines 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.
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.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) 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 & 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. Archives Pathology Lab
Med. 2013;137:1191-1198.
2. Le Chevalier T. Adjuvant Chemotherapy for Resectable
Non-Small-Cell Lung Cancer: Where is it
Going? Ann Oncol. 2010;21:196-8.
3. Datta D, et al. Preoperative Evaluation of Patients
Undergoing Lung Resection Surgery. Chest. 2003;123: 2096-2103.
4. Rangachari, et
al. Brain
Metastasesin Patientswith EGFR-Mutatedor
ALK-RearrangedNon-Small-Cell LungCancers. LungCancer.
2015;88,108-111.
5. Ali A, et
al. Survival of
Patients with Non-small-cell Lung Cancer After a Diagnosis of Brain
Metastases. CurrOncol. 2013;20(4):e300-e306.
6. World
Health Organization. International Agency for Research on Cancer.
Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed September 2020.
7. LUNGevity Foundation. Types of Lung Cancer. Available
at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.
Accessed September 2020.
8. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin
Oncol 2008;26:3552-3559.
9. Sethi S, et al. Incidental Nodule Management - Should There
Be a Formal Process?. Journal of Thorac Onc.
2016:8;S494-S497.
10. LUNGevity Foundation. Screening and Early Detection. Available
at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1.
Accessed September 2020.
Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and
Histological Samples in 11. 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.
12. 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.
13. 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.
14. 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:
21 September
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|