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 February 2024
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 plus chemo approved in US for lung cancer
19 February 2024
Tagrisso with the addition of chemotherapy approved
in the
US for patients with EGFR-mutated advanced lung
cancer
Approval based on FLAURA2 results which showed Tagrisso plus
chemotherapy extended
median progression-free survival by nearly 9 months vs. standard of
care
AstraZeneca's Tagrisso (osimertinib) with the addition of
chemotherapy has been approved in the US for the treatment of
adult patients with locally advanced or metastatic epidermal growth
factor receptor-mutated (EGFRm) non-small cell lung cancer
(NSCLC).
The approval following a Priority
Review by the Food
and Drug Administration (FDA) was based on the results from
the FLAURA2 Phase III trial published in The
New England Journal of Medicine. Tagrisso with
the addition of chemotherapy reduced the risk of disease
progression or death by 38% compared to Tagrisso monotherapy which is the 1st-line global
standard of care (hazard ratio [HR] 0.62; 95% confidence interval
[CI] 0.49-0.79; p<0.0001). Median progression-free survival
(PFS) by investigator assessment was 25.5 months for patients
treated with Tagrisso plus chemotherapy, an 8.8-month improvement
versus Tagrisso monotherapy (16.7
months).
PFS results from blinded independent central review (BICR) were
consistent with the results by investigator assessment, showing
29.4 months median PFS with Tagrisso plus chemotherapy, a 9.5-month improvement
over Tagrisso monotherapy (19.9 months) (HR 0.62; 95% CI
0.48-0.80; p=0.0002).
Each year in the US, there are over 200,000 people diagnosed with
lung cancer, and 80-85% of these patients are diagnosed with NSCLC,
the most common form of lung cancer.1-3 Approximately
70% of people are diagnosed with advanced NSCLC.4 Additionally,
about 15% of NSCLC patients in the US have an EGFR
mutation.5
Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber
Cancer Institute and principal investigator for the
trial, said: "This approval based on the unprecedented data
from FLAURA2 brings a critical new treatment option to patients
with advanced EGFR-mutated non-small cell lung cancer. Now, with
the choice of two highly effective osimertinib-based options,
physicians can better tailor treatment to an individual's needs and
help ensure the best possible outcome for each
patient."
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: "This important new treatment
option can delay disease progression by nearly nine additional
months, establishing a new benchmark with the longest reported
progression-free survival benefit in the 1st-line advanced
setting. This approval
reinforces Tagrisso as
the backbone of EGFR-mutated lung cancer treatment either as
monotherapy or in combination with chemotherapy. This news is
especially important for those with a poorer prognosis, including
patients whose cancer has spread to the brain and those with L858R
mutations."
Laurie Ambrose, President and CEO, GO2 for Lung Cancer, said: "We
are so excited to see this continued progress advancing more
personalized treatment options for our community. The more we can
target the right treatments for the right people at the right time,
the better outcomes will be for our community - a goal we all
collectively share."
Results from a prespecified exploratory analysis of patients in the
FLAURA2 trial with brain metastases at baseline
showed Tagrisso plus chemotherapy reduced the risk of
central nervous system (CNS) disease progression or death by 42%
compared to Tagrisso alone (HR 0.58; 95% CI 0.33-1.01) as
assessed by BICR. With two years of follow up, 74% of patients
treated with Tagrisso plus chemotherapy had not experienced CNS
disease progression or death versus 54% of patients treated
with Tagrisso monotherapy.
While the overall survival (OS) results remained immature at the
second interim analysis (41% maturity), no trend towards a
detriment was observed (HR 0.75; 95% CI 0.57-0.97). The trial
continues to assess OS as a key secondary endpoint.
The safety profile of Tagrisso with the addition of chemotherapy was
generally manageable and consistent with the established profiles
of the individual medicines. Adverse event (AE) rates were higher
in the Tagrisso plus chemotherapy arm, driven by
well-characterised chemotherapy-related AEs. Discontinuation rates
for Tagrisso due to AEs were low in both arms of the
trial (11% for Tagrisso plus chemotherapy and 6% for
monotherapy).
In December 2023, osimertinib (Tagrisso) with the addition of chemotherapy was added to
the NCCN Clinical Practical Guidelines in Oncology (NCCN
Guidelines®) as a NCCN Category 1 Other Recommended regimen
for patients with NSCLC whose tumours have EGFR exon 19 deletion or
exon 21 L858R mutations based on the data from
FLAURA2.6
The US regulatory submission was reviewed under Project
Orbis, which provides a framework for concurrent submission
and review of oncology medicines among participating international
partners. As part of Project Orbis, Tagrisso in combination with chemotherapy is
also under review by regulatory authorities in Australia, Canada,
and Switzerland. Regulatory applications are also under review
in several other countries based on the FLAURA2
results.
Tagrisso is
approved as monotherapy in more than 100 countries including in the
US, EU, China and Japan. Approved indications include for 1st-line
treatment of patients with locally advanced or metastatic EGFRm
NSCLC, locally advanced or metastatic EGFR T790M mutation-positive
NSCLC, and adjuvant treatment of early-stage EGFRm
NSCLC.
As part of AstraZeneca's ongoing commitment to treating patients as
early as possible in lung cancer, Tagrisso is also being investigated in the
neoadjuvant setting in the NeoADAURA Phase III trial with results
expected later this year, and in the early-stage adjuvant
resectable setting in the ADAURA2 Phase III
trial.
Notes
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.7 Lung
cancer is broadly split into NSCLC and small cell lung
cancer.2 The
majority of all NSCLC patients are diagnosed with advanced
disease.4
Patients with EGFRm NSCLC are particularly sensitive to treatment
with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the
cell-signalling pathways that drive the growth of tumour
cells.8
FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III
trial in the 1st-line treatment of patients with locally advanced
(Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients
were treated with Tagrisso 80mg once daily oral tablets with the
addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin
(75mg/m2) or carboplatin (AUC5)) every three weeks for four cycles,
followed by Tagrisso with pemetrexed maintenance every three
weeks.
The trial enrolled 557 patients in more than 150 centres across
more than 20 countries, including in the US, Europe, South America
and Asia. The primary endpoint is PFS. The trial is ongoing and
will continue to assess the secondary endpoint of OS.
Tagrisso
Tagrisso (osimertinib) is
a third-generation, irreversible EGFR-TKI with proven clinical
activity in NSCLC, including against CNS
metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has
been used to treat more than 800,000 patients across its
indications worldwide and AstraZeneca continues to
explore Tagrisso as a treatment for patients across multiple
stages of EGFRm NSCLC.
There is an extensive body of evidence supporting the use
of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve
patient outcomes in both early-stage disease in
the ADAURA Phase III
trial and late-stage
disease in the FLAURA Phase III
trial and FLAURA2 Phase III
trial.
The Company is also researching ways to address tumour mechanisms
of resistance through the SAVANNAH and ORCHARD Phase II trials, and
the SAFFRON Phase III trial, which test Tagrisso plus 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 and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab
deruxtecan in collaboration with Daiichi
Sankyo; Orpathys (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, Rare Diseases, 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 social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here. For Media contacts, click here.
References
1.
ASCO. Lung Cancer - Non-Small Cell: Introduction. Available
at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment.
Accessed February 2024.
2.
LUNGevity Foundation. Types of Lung Cancer. Available
at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed February 2024.
3.
American Cancer Society. What Is Lung Cancer? Available
at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html#:~:text=About%2080%25%20to%2085%25%20of,(outlook)%20are%20often%20similar.
Accessed February 2024.
4. Cagle PT, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab
Med. 2013;137:1191-1198.
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.
NCCN, National Comprehensive Cancer Network® (NCCN®).
Referenced with permission from the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell
Lung Cancer Version 1.2024.© National Comprehensive Cancer
Network, Inc. [2024]. All rights reserved. Accessed [February 14,
2024]. To view the most recent and complete version of the
guideline, go online to NCCN.org. NCCN makes no warranties of any
kind whatsoever regarding their content, use or application and
disclaims any responsibility for their application or use in any
way.
7.
World Health Organisation. 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 February 2024.
8. 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:
19 February 2024
|
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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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