a8050a
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 June 2021
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza reduced recurrence risk in breast cancer
3 June 2021 22:00 BST
Lynparza reduced the risk of cancer recurrence by 42%
in the adjuvant treatment of patients with germline BRCA-mutated
high-risk early breast cancer in OlympiA Phase III
trial
First medicine targeting BRCA mutations to show clinical benefit in
adjuvant setting
Results from the OlympiA Phase III trial showed AstraZeneca and
MSD's Lynparza (olaparib) demonstrated a statistically
significant and clinically meaningful improvement in invasive
disease-free survival (iDFS) versus placebo in the adjuvant
treatment of patients with germline BRCA-mutated (gBRCAm)
high-risk human epidermal growth
factor receptor 2 (HER2)-negative early breast
cancer.
The results will be presented during the plenary session of the
2021 American Society of Clinical Oncology (ASCO) Annual Meeting on
6 June 2021 (abstract LBA#1) and were published today
in The
New England Journal of Medicine.
An estimated 2.3 million people were diagnosed with breast cancer
worldwide in 2020 and BRCA mutations are found in approximately 5%
of breast cancer patients.1,2
Sue Friedman, Executive Director, Facing Our Risk of Cancer
Empowered (FORCE) and member of the OlympiA trial steering
committee, said: "While there have been great strides in the early
treatment of breast cancer, the fear of cancer returning is still
at the forefront of patients' minds. New targeted treatment
approaches are needed in the adjuvant setting that can help keep
cancer and that fear at bay."
Andrew Tutt, chair of the OlympiA trial steering committee and
professor of Oncology at The Institute of Cancer Research, London
and Kings College London, said: "We are thrilled that our global
academic and industry partnership in OlympiA has been able to help
identify a possible new treatment option for patients with
early-stage breast cancer and who have inherited mutations in their
BRCA1 or BRCA2 genes. Patients with early-stage breast cancer who
have inherited BRCA mutations are typically diagnosed at a younger
age compared to those without such a mutation. Olaparib has the
potential to be used as a follow-on to all the standard initial
breast cancer treatments to reduce the rate of life-threatening
recurrence and cancer spread for many patients identified through
genetic testing to have mutations in these genes."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This is the first time that any medicine targeting a BRCA
mutation has demonstrated the potential to change the course of
early-stage breast cancer and offer hope for a cure. By providing a
treatment which significantly reduces the risk of breast cancer
returning in these high-risk patients, we
hope Lynparza will set a new benchmark demonstrating
sustained clinical benefit. We are working with regulatory
authorities to bring Lynparza to these patients as quickly as
possible."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Results of the OlympiA trial represent a potential step
forward for patients with high-risk early breast cancer. These new
data support the importance of testing at diagnosis for BRCA1/2
mutations, which are actionable biomarkers that can help identify
patients with early breast cancer who may be eligible for adjuvant
treatment with Lynparza. Testing for BRCA mutations in addition to
hormone receptor status and the expression of the HER2 protein will
allow clinicians to better inform potential treatment plans for
their patients."
In the overall trial population of patients who had completed local
treatment and standard neoadjuvant or adjuvant chemotherapy,
results showed Lynparza reduced the risk of invasive breast cancer
recurrences, second cancers or death by 42% (based on a hazard
ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82;
p<0.0001). At three years, 85.9% of patients treated
with Lynparza remained alive and free of invasive breast
cancer and second cancers versus 77.1% on
placebo.
Lynparza also demonstrated
a statistically significant and clinically meaningful improvement
in the key secondary endpoint of distant disease-free survival
(DDFS) in the overall trial population. Lynparza reduced the risk of distant disease
recurrence or death by 43% (based on an HR of 0.57; 99.5% CI
0.39-0.83; p<0.0001). At the time of this initial data cut-off,
fewer deaths had occurred in patients
receiving Lynparza, but the difference in overall survival (OS) did
not reach statistical significance. The trial will continue to
assess OS as a secondary endpoint.
In February
2021, the Independent Data
Monitoring Committee recommended for the OlympiA trial to move to
early primary analysis and reporting. Based on the planned interim
analysis, the IDMC concluded that the trial crossed the superiority
boundary for its primary endpoint of iDFS and demonstrated a
sustainable and clinically relevant treatment effect
for Lynparza versus placebo.
Summary of OlympiA results
|
Lynparza
(n=921)
|
Placebo
(n=915)
|
iDFS (primary endpoint)
|
|
HR (99.5% CI)
|
0.58 (0.41, 0.82)
|
p-value
|
p<0.0001
|
iDFS rates
|
|
One year
|
93.3%
|
88.4%
|
Two years
|
89.2%
|
81.5%
|
Three years
|
85.9%
|
77.1%
|
|
DDFS (secondary endpoint)
|
HR (99.5% CI)
|
0.57 (0.39, 0.83)
|
p-value
|
p<0.0001
|
DDFS rates
|
|
One year
|
94.3%
|
90.2%
|
Two years
|
90.0%
|
83.9%
|
Three years
|
87.5%
|
80.4%
|
|
OS at interim (secondary endpoint)ii
|
HR (99% CI)
|
0.68 (0.44, 1.05)
|
p-value
|
p=0.024
|
OS rates
|
|
One year
|
98.1%
|
96.9%
|
Two years
|
94.8%
|
92.3%
|
Three years
|
92.0%
|
88.3%
|
i The data
cut-off date for the interim analysis was 27 March
2020.
ii Statistical significance not reached based on the interim
analysis plan for alpha conservation for future survival
analyses.
The safety and tolerability profile of Lynparza in
this trial was in line with that observed in prior clinical trials.
The most common adverse events (AEs) were nausea (57%), fatigue
(40%), anaemia (23%) and vomiting (23%). Grade 3 or higher AEs
were anaemia (9%), neutropenia (5%), leukopenia (3%), fatigue
(2%), and nausea (1%). Approximately 10% of patients treated
with Lynparza discontinued
treatment early due to AEs.
OlympiA is a global collaborative Phase III trial coordinated by
the Breast International Group (BIG) worldwide, in partnership with
NRG Oncology, the US National Cancer Institute (NCI), Frontier
Science & Technology Research Foundation (FSTRF), AstraZeneca
and MSD.3 The
trial is sponsored by NRG Oncology in the US and by AstraZeneca
outside the US.
Lynparza is approved in
the US, Japan, and a number of other countries for gBRCAm,
HER2-negative, metastatic breast cancer previously treated with
chemotherapy; in the EU, this includes locally advanced breast
cancer.
Early breast cancer
Breast cancer is the most common cancer among women worldwide and
an estimated 70% of all breast cancer is
diagnosed at an early stage.4,5 Breast
cancer is one of the most biologically diverse tumour types with
various factors underlying its development and
progression.6 The
discovery of biomarkers in the development of breast
cancer has greatly impacted scientific understanding of the
disease and treatment of patients who develop the
disease.7
OlympiA
OlympiA is a Phase III, double-blind, placebo-controlled,
multicentre trial testing the efficacy and safety
of Lynparza tablets versus placebo as adjuvant treatment
in patients with gBRCAm, high-risk, HER2-negative early breast
cancer, who have completed definitive local treatment and
neoadjuvant or adjuvant chemotherapy. The primary endpoint of the
trial is iDFS defined as time from randomisation to date of first
loco-regional or distant recurrence, new cancer or death from any
cause. Key secondary endpoints include OS and DDFS, which is
defined as time from randomisation until documented evidence of
first distant recurrence of breast cancer or death without distant
recurrence.3
BIG
The Breast International Group (BIG) is an international
not-for-profit organisation for academic breast cancer research
groups from around the world, based in Brussels,
Belgium.
Founded by leading European opinion leaders in 1999, the
organisation aims to address fragmentation in breast cancer
research and now represents a network of over 50 like-minded
research groups affiliated with specialised hospitals, research
centres and leading experts across approximately 70 countries on
six continents.
BIG's research is supported in part by its philanthropy unit, known
as BIG against breast cancer, which is used to interact with the
general public and donors, and to raise funds for BIG's purely
academic breast cancer trials and research programmes.
FSTRF
Frontier Science & Technology Research Foundation (FSTRF) is a
non-profit, research organisation which supports research networks,
pharmaceutical companies and investigators to conduct
scientifically meaningful high-quality clinical trials. The OlympiA
trial involved research staff in the US and in the Affiliate office
in Scotland.
FSTRF works with scientists and technicians in more than 800
laboratories, universities and medical centres around the world to
provide a comprehensive range of research services throughout the
clinical trial process including design, analysis and
reporting.
Through its work, FSTRF aims to advance the application of
statistical science and practice and data management techniques in
science, healthcare and
education.
NRG Oncology
NRG Oncology is a network group funded by the US National Cancer
Institute (NCI), a part of the National Institutes of Health. NRG
Oncology brings together the National Surgical Adjuvant Breast and
Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG),
and the Gynecologic Oncology Group (GOG), with the mission to
improve the lives of cancer patients by conducting
practice-changing multi-institutional clinical and translational
research. NRG Oncology sponsored OlympiA in the US and collaborated
with the other adult cancer clinical trials research groups funded
by the NCI, Alliance, ECOG/ACRIN and the Southwest Oncology Group.
The NCI and AstraZeneca are collaborating under a Cooperative
Research and Development Agreement between the
parties.
BRCA1 and BRCA2
BRCA1 and BRCA2 are human genes that produce proteins responsible
for repairing damaged DNA and play an important role maintaining
the genetic stability of cells. When either of these genes is
mutated or altered such that its protein product either is not made
or does not function correctly, DNA damage may not be repaired
properly, and cells become unstable. As a result, cells are more
likely to develop additional genetic alterations that can lead to
cancer and confer sensitivity
to PARP inhibitors including Lynparza.8-11
Lynparza
Lynparza (olaparib) is a
first-in-class PARP inhibitor and the first targeted treatment to
block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in homologous recombination repair (HRR), such as
mutations in BRCA1 and/or BRCA2. Inhibition of PARP
with Lynparza leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death. Lynparza is being tested in a range of PARP-dependent
tumour types with defects and dependencies in the DDR
pathway.
Lynparza is currently
approved in a number of countries, including those in the EU, for
the maintenance treatment of platinum-sensitive relapsed ovarian
cancer. It is approved in the US, the EU, Japan, China, and several
other countries as 1st-line maintenance treatment of BRCA-mutated
advanced ovarian cancer following response to platinum-based
chemotherapy. It is also approved in the US, EU and Japan as a
1st-line maintenance treatment with bevacizumab for patients with
HRD-positive advanced ovarian cancer (BRCAm and/or genomic
instability). Lynparza is approved in the US, Japan, and a number
of other countries for germline BRCA-mutated, HER2-negative,
metastatic breast cancer, previously treated with chemotherapy; in
the EU, this includes locally advanced breast cancer. It is also
approved in the US, the EU, Japan and several other countries for
the treatment of germline BRCAm metastatic pancreatic
cancer. Lynparza is approved in the US for HRR gene-mutated
metastatic castration-resistant prostate cancer (BRCAm and other
HRR gene mutations) and in the EU and Japan for BRCAm metastatic
castration-resistant prostate cancer. Regulatory reviews are
underway in several countries for ovarian, breast, pancreatic and
prostate cancers.
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, has
been used to treat over 40,000 patients
worldwide. Lynparza has the broadest and most advanced clinical
trial development programme of any PARP inhibitor, and AstraZeneca
and MSD are working together to understand how it may affect
multiple PARP-dependent tumours as a monotherapy and in combination
across multiple cancer types. Lynparza is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise Lynparza,
the world's first PARP inhibitor, and Koselugo (selumetinib),
a mitogen-activated protein kinase (MEK) inhibitor, for
multiple cancer types. Working together, the companies will
develop Lynparza and Koselugo in
combination with other potential new medicines and as
monotherapies. Independently, the companies will
develop Lynparza and Koselugo in
combination with their respective PD-L1 and PD-1
medicines.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, the current
clinical paradigm for how breast cancer is classified and treated
to deliver even more effective treatments to patients in need -
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising
compounds in development that leverage different mechanisms of
action to address the biologically diverse breast cancer tumour
environment. AstraZeneca aims to continue to transform outcomes for
HR-positive breast cancer with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation SERD and
potential new medicine camizestrant. PARP
inhibitor, Lynparza (olaparib) is a targeted treatment option
for metastatic breast cancer patients with an inherited BRCA
mutation. AstraZeneca with MSD continue to
research Lynparza in metastatic breast cancer patients with an
inherited BRCA mutation and are exploring new opportunities to
treat these patients earlier in their disease
state.
Building on the first approval of Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody-drug conjugate (ADC), in previously treated HER2-positive
metastatic breast cancer, AstraZeneca and Daiichi Sankyo are
exploring its potential in earlier lines of treatment and in new
breast cancer settings. To bring much needed treatment options to
patients with triple-negative breast cancer, an aggressive form of
breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other
oncology medicines, including Lynparza and Enhertu, assessing the potential of AKT kinase inhibitor,
capivasertib, in combination with chemotherapy, and collaborating
with Daiichi Sankyo to explore the potential of TROP2-directed ADC,
datopotamab deruxtecan.
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. World Health Organization. Estimated number of cases in 2020,
worldwide, both sexes, all ages. Available
at: https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf. Accessed
May 2021.
2. Mitri Z, et al. The HER2 Receptor in Breast Cancer:
Pathophysiology, Clinical Use, and New Advances in
Therapy. Chemother Res
Pract.
2012;743193.
3. ClinicalTrials.gov. Olaparib as Adjuvant Treatment in Patients
with Germline BRCA-mutated High Risk HER2 Negative Primary Breast
Cancer (OlympiA). Available at clinicaltrials.gov/ct2/show/NCT02032823.
Accessed May 2021.
4. Breast Cancer School. Will I survive breast cancer? Available
at: https://www.breastcancercourse.org/will-i-survive-breast-cancer/.
Accessed May 2021.
5. Bertozzi S, et al. Biomarkers in Breast
Cancer. Intechopen. 2018.
6. Yersal O, and Barutca S. Biological Subtypes of Breast Cancer:
Prognostic and therapeutic implications. World J Clin
Oncol.
2014;5(3):412-424.
7. Rivenbark A, et al. Molecular and Cellular Heterogeneity in Breast
Cancer: Challenges for Personalized
Medicine. Am J Pathol. 2013;183(4):1113-1124.
8. Roy R, et al. BRCA1 and BRCA2: Different Roles in a Common
Pathway of Genome Protection. Nat Rev
Cancer.
2021;12(1):68-78.
9. Wu J, et al. The Role of BRCA1 in DNA Damage
Response. Protein
Cell.
2010;1(2):117-11.
10. Gorodetska I, et al. BRCA Genes: The Role in Genome Stability,
Cancer Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.
11. Li H, et al. PARP Inhibitor Resistance: The Underlying
Mechanisms and Clinical Implications. Mol Cancer. 2020;19:107.
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:
04 June
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|