a3346j
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 December 2020
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 US for the adjuvant treatment of patients
with early-stage EGFR-mutated lung cancer
21 December 2020 07:05
GMT
Tagrisso approved in the US 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 US
for the adjuvant treatment of adult patients with early-stage
epidermal growth factor receptor-mutated (EGFRm) non-small cell
lung cancer (NSCLC) after tumour resection with curative
intent. Tagrisso is indicated for EGFRm patients whose
tumours have exon 19 deletions or exon 21 L858R mutations as
detected by an approved test.
The approval was granted under the US Food and Drug
Administration's (FDA) Real-Time Oncology Review (RTOR) pilot
program. Five other countries participated in a concurrent
submission and review process through FDA's Project
Orbis.
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 and nearly half of patients
diagnosed in Stage IB, and over three quarters of patients
diagnosed in Stage IIIA, experience recurrence within five
years.1-4
The approval was based on results from the ADAURA Phase III
trial where 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, and also in the overall trial population of patients
with Stage IB-IIIA disease, a key secondary
endpoint.
Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer
Center and Smilow Cancer Hospital, New Haven, CT and principal
investigator in the ADAURA Phase III trial, said:
"Adjuvant Tagrisso has demonstrated an unprecedented
disease-free survival benefit for early-stage lung cancer patients
with EGFR mutations who face high rates of recurrence even after
successful surgery and subsequent chemotherapy. This approval
reinforces how critical it is to test all lung cancer patients for
EGFR mutations before deciding how to treat them and regardless of
their stage at diagnosis. This will help ensure as many patients as
possible can benefit from this potentially practice-changing
treatment."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "For the first time, a targeted, biomarker-driven treatment
option is available to patients in the US with early-stage
EGFR-mutated lung cancer. This approval dispels the notion that
treatment is over after surgery and chemotherapy, as the ADAURA
results show that Tagrisso can dramatically change the course of this
disease. We remain committed to treating cancer patients earlier,
when they may still have a chance of being
cured."
Adjuvant treatment with Tagrisso reduced the risk of disease recurrence or
death by 83% in the primary endpoint of DFS in patients with Stage
II and IIIA disease (hazard ratio [HR] 0.17; 95% confidence
interval [CI] 0.12-0.23; p<0.0001). DFS results in the overall
trial population of patients with Stage IB-IIIA disease
showed Tagrisso reduced the risk of disease recurrence or
death by 80% (HR 0.20; 95% CI 0.15-0.27; p<0.0001). At two
years, 89% of patients treated with Tagrisso remained alive and disease free versus 52%
on placebo after surgery, the current standard of care. The safety
and tolerability of Tagrisso in
this trial was consistent with previous trials in the
metastatic setting.
Tagrisso was recently
granted Breakthrough Therapy
Designation for patients
in the early-stage disease setting by the US FDA.
In April
2020, an Independent Data
Monitoring Committee recommended for the ADAURA trial to be
unblinded two years early based on a determination of overwhelming
efficacy. Investigators and patients continue to participate in the
trial and remain blinded to treatment. The results from the ADAURA
trial were presented during the plenary session of the American
Society of Clinical Oncology ASCO20 Virtual Scientific Program in
May 2020 and were recently published in The
New England Journal of Medicine.
The US regulatory submission was reviewed under the FDA's RTOR
pilot program which aims to ensure that safe and effective
treatments are available to patients as early as possible. Five
national health authorities collaborated with the FDA on this
review through Project Orbis, an initiative of the FDA Oncology
Center of Excellence, which provides a framework for concurrent
submission and review of oncology medicines among international
partners. These included Health Canada, the Australian Therapeutic
Goods Administration, the Brazilian Health Regulatory Agency
(Anvisa), Swissmedic, and Singapore Health Sciences
Authority. The UK Medicines and Healthcare products Regulatory
Agency participated in the review as an observer.
In China, Tagrisso is under priority review for the adjuvant
treatment of patients with early-stage EGFRm NSCLC based on the
ADAURA Phase III trial. This indication is also under regulatory
review in the EU and additional global submission discussions are
ongoing.
Tagrisso is a once-daily
oral tablet 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.5 Lung
cancer is broadly split into NSCLC and small cell lung cancer, with
80-85% classified as NSCLC.6 The
majority of all NSCLC patients are diagnosed with advanced disease
while approximately 25-30% present with resectable disease at
diagnosis.1-3
For patients with resectable tumours, the majority of patients
eventually develop recurrence despite complete tumour resection and
adjuvant chemotherapy.4 Early-stage
lung cancer diagnoses are often only made when the cancer is found
on imaging for an unrelated condition.7-8
Approximately 10-15% of NSCLC patients in the US and Europe, and
30-40% of patients in Asia have EGFRm NSCLC.9-11 These
patients are particularly sensitive to treatment with an
EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the
cell-signalling pathways that drive the growth of tumour
cells.12
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 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.
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 six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- 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/Nasdaq: 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. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin
Oncol 2008;26:3552-3559.
5. 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 August 2020.
6. LUNGevity Foundation. Types of Lung Cancer. Available
at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.
Accessed August 2020.
7. Sethi S, et al. Incidental Nodule Management - Should There
Be a Formal Process?. Journal of Thorac Onc.
2016:8;S494-S497.
8. LUNGevity Foundation. Screening and Early Detection. Available
at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1.
Accessed August 2020.
9. 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.
10. 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.
11. 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.
12. 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 December
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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