TIDMAZN
RNS Number : 4496M
AstraZeneca PLC
11 May 2020
11 May 2020 07:00 BST
Lynparza approved in the US as 1st-line maintenance
treatment
with bevacizumab for HRD-positive advanced ovarian cancer
Patients treated with Lynparza and bevacizumab lived without
disease progression for 37.2 months vs. 17.7 months median for
bevacizumab alone
One in two women with advanced ovarian cancer has an
HRD-positive tumour
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as
Merck & Co., Inc. inside the US and Canada) today announced
that Lynparza (olaparib) in combination with bevacizumab has been
approved in the US 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 and whose cancer is associated
with homologous recombination deficiency (HRD) positive status
defined by either a deleterious or suspected deleterious BRCA
mutation, and/or genomic instability. Patients will be selected for
therapy based on an FDA-approved companion diagnostic test.
The approval by the US Food and Drug Administration (FDA) was
based on a biomarker subgroup analysis of the Phase III PAOLA-1
trial which showed that Lynparza in combination with bevacizumab
maintenance treatment reduced the risk of disease progression or
death by 67% (equal to a hazard ratio of 0.33). The addition of
Lynparza improved progression-free survival (PFS) to a median of
37.2 months versus 17.7 months with bevacizumab alone in patients
with HRD-positive advanced ovarian cancer.
Approximately one in two women with advanced ovarian cancer has
an HRD-positive tumour. For patients with advanced ovarian cancer,
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.
Isabelle Ray-Coquard, principal investigator of the PAOLA-1
trial and medical oncologist, Centre Léon Bérard and President of
the GINECO group, said: "Ovarian cancer is a devastating disease.
The magnitude of benefit in HRD-positive patients in the PAOLA-1
trial is impactful. The combination of Lynparza and bevacizumab now
provides women with HRD-positive advanced ovarian cancer with a new
standard of care and I look forward to seeing this translate into
clinical practice."
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, said: "This approval represents another milestone for
Lynparza in patients with ovarian cancer. The median
progression-free survival of more than three years offers new hope
for more women to delay relapse in this difficult-to-treat disease.
These results further establish that HRD-positive is a distinct
subset of ovarian cancer, and HRD testing is now a critical
component for the diagnosis and tailoring of treatment for women
with advanced ovarian cancer."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Advances in understanding the role of biomarkers and PARP
inhibition have fundamentally changed how physicians treat this
aggressive type of cancer. Today's approval based on the PAOLA-1
trial highlights the importance of HRD testing at diagnosis to
identify those who may benefit from Lynparza in combination with
bevacizumab as a 1st-line maintenance treatment."
The full results from the Phase III PAOLA-1 trial were published
in The New England Journal of Medicine .
Regulatory reviews are currently underway in the EU, Japan and
other countries for Lynparza based on results from the PAOLA-1
trial. As part of a broad development programme, Lynparza is being
tested as a monotherapy and in combination across multiple tumour
types including as a potential adjuvant treatment of patients with
germline BRCA-mutated high-risk HER2-negative primary breast cancer
in the Phase III OlympiA trial.
Financial considerations
Following this approval for Lynparza in the US, AstraZeneca will
receive from MSD $100m in Collaboration Revenue, anticipated to be
booked by the Company during the second quarter of 2020.
Ovarian cancer
Ovarian cancer is the eighth most common cause of death from
cancer in women worldwide. (1) In 2018, there were nearly 300,000
new cases diagnosed and around 185,000 deaths. (2) Most women are
diagnosed with advanced (Stage III or IV) ovarian cancer and have a
five-year survival rate of approximately 30%. (3) Approximately 50%
of ovarian cancers are HRD-positive including BRCA1/2 mutation.
(4,5) Some 22% of ovarian cancers have a BRCA1/2 mutation. (5)
For patients with advanced ovarian cancer, the primary aim of
1st-line treatment is to delay progression of the disease for as
long as possible and maintain the patient's quality of life with
the intent of achieving complete remission. (6,7,8,9)
In the US, bevacizumab was approved for use in combination with
chemotherapy for the 1st-line treatment of advanced ovarian cancer
in 2018. Within two years nearly half of all patients with advanced
ovarian cancer are receiving this combination treatment. (10)
PAOLA-1
PAOLA-1 is a double-blind Phase III trial testing the efficacy
and safety of Lynparza in combination with bevacizumab vs.
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.
Simultaneously, the Myriad Genetics myChoice CDx test has been
approved in the US as a companion diagnostic for Lynparza in this
new indication.
Homologous recombination deficiency
HRD, which defines a sub-group 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. (5)
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, 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, 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. Lynparza is approved in the US and
several other countries for the treatment of germline BRCA-mutated
metastatic pancreatic cancer. Regulatory reviews are underway in
several jurisdictions 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 30,000 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 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 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 six 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. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
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 and Metabolism, and Respiratory and
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. Cancer.org. (2020). Ovarian Cancer Statistics | How Common Is Ovarian Cancer. Available at: www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html . [Accessed March 2020].
2. The World Health Organization. IARC. Globocan 2018. Available
at: http://gco.iarc.fr/ [Accessed March 2020].
3. National Cancer Institute. (2019). Cancer Stat Facts: Ovarian Cancer Available at:
https://seer.cancer.gov/statfacts/html/ovary.html [Accessed March 2020].
4. Moschetta et al. (2016). BRCA somatic mutations and
epigenetic BRCA modifications in serous ovarian cancer. Annals of
Oncology, 27(8), pp.1449-1455.
5. da Cunha Colombo Bonadio et al. (2018). Homologous
recombination deficiency in ovarian cancer: a review of its
epidemiology and management. Clinics (Sao Paulo). 2018;73(suppl
1):e450s.
6. Moore, K. (2018). Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine,
379(26), pp.2495-2505.
7. Raja et al. 2012. Optimal first-line treatment in ovarian
cancer. Annals on Oncology. 23 Suppl 10, x118-127.
8. NHS Choices, Ovarian Cancer Available at:
https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed March 2020].
9. Ledermann et al. (2013). Newly diagnosed and relapsed
epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up. Annals of Oncology, 24,
pp.vi24-vi32.
10. AstraZeneca data on file. Kantar Health, Q1 2020.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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