a2781a
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 2022
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza approved in China for ovarian cancer
22 September 2022 07:00 BST
Lynparza approved
in China as 1st-line maintenance treatment with bevacizumab for
HRD-positive advanced ovarian cancer
One in two women with advanced ovarian cancer has an HRD-positive
tumour
AstraZeneca and MSD's Lynparza (olaparib) has been approved in China
for the
maintenance treatment of adult patients with advanced epithelial
ovarian, fallopian tube or primary peritoneal cancer who are in
complete or partial response to 1st-line platinum-based
chemotherapy in combination with bevacizumab, and whose cancer is
associated with homologous recombination deficiency (HRD)-positive
status.
In China, ovarian cancer is the third most common gynaecologic
cancer, with a five-year survival rate of approximately
39%, largely
because more than 70% of women are diagnosed with advanced disease
(Stage III or IV).1,2 In
2020, there were over 55,000 new cases of ovarian cancer in
China.3
The approval by China's National Medical Products Administration
was based on an HRD-positive subgroup exploratory analysis of the
PAOLA-1 Phase III trial which showed Lynparza plus bevacizumab demonstrated a substantial
progression-free survival (PFS) improvement versus bevacizumab
alone for patients with HRD-positive advanced ovarian cancer.
During European Society for Medical Oncology Congress (ESMO)
2022, the
final overall survival (OS) results were
presented from the PAOLA-1 Phase III trial demonstrating
that Lynparza plus bevacizumab provided a clinically
meaningful improvement in overall survival in HRD-positive advanced
ovarian cancer.
Professor Ding Ma, Member of the Chinese Academy of Engineering,
said: "Ovarian cancer has the highest fatality rate among
gynaecologic cancers in China. The emergence of PARP inhibitors and
their application in the 1st-line treatment of ovarian cancer could
help patients delay disease progression and achieve long-term
remission. In the PAOLA-1 trial, the combination of olaparib and
bevacizumab demonstrated clinically
meaningful improvements in overall survival. This
approval provides
HRD-positive patients with a new option for 1st-line maintenance
therapy."
Professor Beihua Kong, Chairman of the Gynaecological Oncology
Branch of the Chinese Medical Association, said: "Ovarian cancer
has entered the era of precision medicine, and HRD detection
(including BRCA1/2 mutations) has important clinical value for
newly diagnosed patients with advanced ovarian cancer, to help
guide first-line treatment decisions. The approval of the
combination of olaparib and bevacizumab brings a clinically
meaningful survival benefit to HRD-positive patients, and further
reflects the importance of a precision approach to help guide
treatment decisions in ovarian cancer."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "The maintenance treatment
of Lynparza in combination with bevacizumab has shown to
both improve progression-free survival and provide a clinically
meaningful improvement in overall survival in patients with
HRD-positive advanced ovarian cancer following response to
platinum-based chemotherapy. I am thrilled we can now bring this
targeted treatment option to these patients in
China."
Dr Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, MSD Research Laboratories,
said: "This approval is an important milestone for patients
with newly diagnosed advanced ovarian cancer in China and
underscores the critical importance of HRD testing for all women
with advanced ovarian cancer at the point of
diagnosis."
The initial results from
the PAOLA-1 Phase III trial showed
that Lynparza plus bevacizumab reduced the risk of disease
progression or death by 67% in the subgroup of patients with
HRD-positive advanced ovarian cancer (based on a hazard ratio [HR]
of 0.33; 95% confidence interval [CI] 0.25-0.45 from the
pre-specified exploratory analysis). Lynparza plus bevacizumab also improved PFS to a
median of 46.8 versus 17.6 months with bevacizumab alone in this
patient population. The primary endpoint in the intent-to-treat
population was a statistically significant and clinically
meaningful improvement in PFS. The data from the PAOLA-1 trial was
published in The
New England Journal of Medicine in
2019.
Further results from
the five-year analysis of the PAOLA-1 trial recently presented at
the ESMO 2022 showed Lynparza plus bevacizumab increased median overall
survival to 56.5 months versus 51.6 months with bevacizumab alone,
in patients with newly diagnosed advanced ovarian cancer
irrespective of HRD status. This increase was not statistically
significant. In HRD-positive patients, Lynparza plus bevacizumab provided a clinically
meaningful improvement in overall survival, reducing the risk of
death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI
0.45-0.85 from the pre-specified exploratory sub-group analysis)
despite PAOLA-1 having 30% Stage IV patients. The
safety and tolerability profile of Lynparza in this trial was in line with that observed
in prior clinical trials, with no new safety
signals.
Lynparza in combination
with bevacizumab is approved in the
US, and several other
countries as a 1st-line maintenance treatment for patients with
HRD-positive advanced ovarian cancer and is currently under
regulatory review in other countries around the world. In
China, Lynparza is approved for
the treatment of BRCA-mutated metastatic castration-resistant
prostate cancer as well as a 1st-line maintenance therapy
in BRCA-mutated
advanced ovarian cancer.
Notes
Ovarian cancer
Ovarian cancer is the eighth most common cancer in women
worldwide.4 There
were more than 313,000 new cases of ovarian cancer in 2020, and
over 207,000 deaths. The 5-year survival rate of newly
diagnosed advanced ovarian cancer patients has typically been
30-50%.5,6 Roughly
half of women with advanced ovarian cancer have homologous
recombination deficiency (HRD)-positive tumours including those
with a BRCA mutation and up to one in five women have a BRCA
mutation.7-9 The
primary aim of 1st-line treatment is to delay disease progression
for as long as possible with the intent to achieve long-term
remission.10-12
PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy
and safety of Lynparza added to standard of care bevacizumab
versus bevacizumab alone, as a 1st-line maintenance treatment for
newly diagnosed advanced FIGO Stage III-IV high-grade serous or
endometroid ovarian, fallopian tube, or peritoneal cancer patients
who had a complete or partial response to 1st-line treatment with
platinum-based chemotherapy and bevacizumab. AstraZeneca and
MSD announced
in August 2019 that
the trial met its primary endpoint of PFS in the overall trial
population.
The primary analysis of the PAOLA-1 Phase III trial showed
that Lynparza, in combination with bevacizumab maintenance
treatment, reduced the risk of disease progression or death by 67%
(based on a HR of 0.33; 95% CI 0.25-0.45) in the subgroup of
patients with HRD-positive advanced ovarian cancer. The addition
of Lynparza improved PFS to a median of 46.8 months
versus 17.6 with bevacizumab alone in this patient
population.
Updated results from the five-year analysis of the PAOLA-1 Phase
III trial demonstrate that in a pre-specified exploratory subgroup
analysis of HRD-positive patients, Lynparza plus bevacizumab provided a clinically
meaningful improvement in overall survival, reducing the risk of
death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI
0.45-0.85). In addition, 65.5% of patients treated
with Lynparza plus bevacizumab were still alive at five
years versus 48.4% of those treated with bevacizumab
alone. Lynparza plus bevacizumab also improved median PFS to
almost four years (46.8 months) versus 17.6 months with bevacizumab
plus placebo, and 46.1% of patients treated
with Lynparza plus bevacizumab remain progression free at
five years versus 19.2% of patients treated with bevacizumab
alone.
PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological
Trial groups) trial, sponsored by ARCAGY Research (Association de
Recherche sur les CAncers dont GYnécologiques) on behalf of
GINECO (Groupe d'Investigateurs National des Etudes des Cancers
Ovariens et du sein), lead group for the PAOLA-1 trial.
ARCAGY-GINECO is an academic group specialising in clinical and
translational research in patients' gynaecological cancers,
labelled by the French National Cancer Institute (INCa), and a
member of the GCIG (Gynecologic Cancer InterGroup).
Homologous recombination deficiency
HRD, which defines a subgroup of ovarian cancer, encompasses a wide
range of genetic abnormalities, including BRCA mutations and
beyond. As with BRCA gene mutations, HRD interferes with normal
cell DNA repair mechanisms and confers sensitivity to PARP
inhibitors including Lynparza.13
Lynparza
Lynparza (olaparib)
is a 1st-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 across multiple tumour
types including maintenance treatment of platinum-sensitive
relapsed ovarian cancer and as both monotherapy and in combination
with bevacizumab for the 1st-line maintenance treatment of
BRCA-mutated (BRCAm) and HRD-positive advanced ovarian cancer,
respectively; for gBRCAm, HER2-negative metastatic breast cancer
(in the EU and Japan this includes locally advanced breast cancer);
for gBRCAm, HER2-negative high-risk early breast cancer (in Japan
this includes all BRCAm HER2-negative high-risk early breast
cancer); for gBRCAm metastatic pancreatic cancer; and HRR
gene-mutated metastatic castration-resistant prostate cancer (BRCAm
only in the EU and Japan). In
China, Lynparza is approved for
the treatment of BRCA-mutated metastatic castration-resistant
prostate cancer as well as a 1st-line
maintenance therapy in BRCA-mutated
advanced ovarian cancer.
Lynparza, which
is being jointly developed and commercialised by AstraZeneca and
MSD, has been used to treat over 75,000 patients
worldwide. Lynparza has a broad clinical trial development
programme, 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 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 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.
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
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References
1. Jiang X, et al. Epidemiology of gynecologic cancers in
China. J Gynecol
Oncol. 2018 Jan; 29(1):
e7.
2. Bu H, et al. BRCA mutation frequency and clinical
features of ovarian cancer patients: A report from a Chinese study
group. J Obstet Gynaecol
Res. 2019
Nov;45(11):2267-2274.
3. Globocan. China Globocan 2020.
Available at https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
Accessed September 2022.
4. Momenimovahed
Z, et
al. Ovarian Cancer in The
World: Epidemiology And Risk Factors. Int J Womens
Health. 2019 Apr
30;11:287-299.
5. Torre
A, et
al. Ovarian
Cancer Statistics. CA Cancer J
Clin. 2018
Jul; 68(4):284-296.
6. National Cancer
Institute. Cancer Stat Facts: Ovarian Cancer. Available
at https://seer.cancer.gov/statfacts/html/ovary.html. Accessed
September 2022.
7. Pothuri B. BRCA1- and BRCA2-related
mutations: therapeutic implications in ovarian
cancer. Ann of
Oncol.
2018;24(8):822-827.
8. Moschetta
M, et
al. BRCA somatic
mutations and epigenetic BRCA modifications in serous ovarian
cancer. Ann Oncol. 2016 Aug;27(8):1449-55.
9. Bonadio R, et al. Homologous recombination deficiency in
ovarian cancer: a review of its epidemiology and
management. Clinics (Sao Paulo). 2018 Aug 20;73(suppl
1):e450s.
10. Raja F, et al. Optimal first-line treatment in ovarian
cancer. Ann of
Oncol.
2012;23(10):118-127.
11. NHS Choices, Ovarian
Cancer Available at https://www.nhs.uk/conditions/ovarian-cancer/treatment/. Accessed
September 2022.
12. Ledermann J, et al. Newly diagnosed and relapsed epithelial
ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi24-32.
13. Moore
K, et
al. Maintenance Olaparib in
Patients with Newly Diagnosed Advanced Ovarian
Cancer. New England
Journal of Medicine. 2019;379(26),
pp.2495-2505.
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:
22 September 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|