# AstraZeneca Lynparza approved in China for BRCA-mutated advanced ovarian cancer

- Link: https://www.directorstalkinterviews.com/astrazeneca-lynparza-approved-in-china-for-brca-mutated-advanced-ovarian-cancer/412799978
- Published: 2019-12-05T07:15:03+00:00
- Author: Amilia Stone

**AstraZeneca** ([LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US
and Canada) today announced that the companies have received marketing authorisation
from China’s National Medical Products Administration for _Lynparza_ as a 1st-line
maintenance treatment of adult patients with newly diagnosed advanced germline or
somatic BRCA mutated epithelial ovarian, fallopian tube or primary peritoneal cancer
who are in complete or partial response to 1st-line platinum-based chemotherapy.

The approval in China is based on the results from the Phase III SOLO-1 trial, which
were published in The New England Journal of Medicine_._ Results showed that _Lynparza_
significantly reduced the risk of disease progression or death by 70% (equal to 
a hazard ratio of 0.30) vs. placebo in women with BRCAm advanced ovarian cancer 
following response to platinum-based chemotherapy. Of those women receiving _Lynparza_,
60% remained progression-free at three years vs. 27% of women receiving placebo.

For newly diagnosed advanced ovarian cancer patients, the primary aim of treatment
is to delay progression of the disease for as long as possible, with the intent 
of achieving complete remission or cure. Of women diagnosed with ovarian cancer,
15% have a germline (inherited) mutation and 7% have a somatic (acquired) mutation
in their BRCA1/2 genes.

> **Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: **“
> This approval marks a new era for women with BRCA-mutated advanced ovarian cancer
> in China, where the prevalence of BRCA mutations in advanced disease is higher
> than the international average. Currently, 70% of women relapse within three years
> of initial treatment, representing the highest reoccurrence rate among gynaecological
> cancers worldwide. The progression-free survival benefit of _Lynparza_ observed
> in SOLO-1 is a significant step towards helping these women achieve long-term 
> remission.”

> **Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief
> Medical Officer, MSD Research Laboratories, said: **“Today’s approval of _Lynparza_
> reinforces the importance of patients knowing their BRCA mutation status at diagnosis.
> We are proud to provide a new option for the treatment of this devastating disease
> in China, and we will continue to collaborate with the Chinese government and 
> healthcare organisations to provide _Lynparza_ to patients who need it as quickly
> as possible.”

_Lynparza_ is the first PARP inhibitor approved in China for 1st-line maintenance
in BRCAm advanced ovarian cancer**.** AstraZeneca and MSD are exploring additional
trials in ovarian cancer and recently announced positive results from the Phase 
III PAOLA-1 trial, which tested _Lynparza_ in combination with bevacizumab as a 
1st-line maintenance treatment for women with newly-diagnosed advanced ovarian cancer,
regardless of their biomarker status or surgical outcome.

**About SOLO-1**

SOLO-1 was a Phase III, randomised, double-blinded, placebo-controlled, multi-centre
trial to evaluate the efficacy and safety of _Lynparza_ tablets (300mg twice daily)
as a maintenance monotherapy compared with placebo in patients with BRCAm advanced
ovarian cancer following 1st-line platinum-based chemotherapy. The trial randomised
391 patients with a deleterious or suspected deleterious germline or somatic BRCA1
or BRCA2 mutation who were in clinical complete or partial response following platinum-
based chemotherapy.

Patients were randomised (2:1) to receive _Lynparza_ or placebo for up to two years
or until disease progression. Patients who had a partial response at two years were
permitted to stay on therapy at the investigator’s discretion. The primary endpoint
was progression-free survival (PFS) and key secondary endpoints included time to
second disease progression or death, time to first subsequent treatment and overall
survival.

The SOLO-1 safety profile was in line with that observed in prior clinical trials,
and with no detriment to quality of life. The most common adverse events (AEs) ≥
20% were nausea (77%), fatigue (63%), vomiting (40%), anaemia (39%) and diarrhoea(
34%). The most common ≥ Grade 3 AEs were anaemia (22%) and neutropenia (9%). Some
71% of patients on _Lynparza_ remained on the recommended starting dose. Additionally,
88% of patients on _Lynparza_ continued treatment without an AE-related discontinuation.

The data were presented on 21 October 2018, at the Presidential Symposium of the
European Society of Medical Oncology (ESMO) 2018 Congress in Munich, Germany.

**About ovarian cancer**

Ovarian cancer is the eighth most common cause of death from cancer in women worldwide.
In 2018, there were nearly 300,000 new cases diagnosed and around 185,000 deaths.
^(1) China has the highest prevalence of ovarian cancer globally, with more than
52,000 new cases diagnosed in 2018 and approximately 30,886 deaths.^(1,2) Most women
are diagnosed with advanced (Stage III or IV) ovarian cancer and have a five-year
survival rate of approximately 30%.^(3) Of women diagnosed with ovarian cancer, 
15% have a germline mutation and 7% have a somatic mutation in their BRCA1/2 genes.
^(4,5) For newly-diagnosed advanced ovarian cancer, the primary aim of treatment
is to delay progression of the disease for as long as possible with the intent of
achieving complete remission or cure.^(6,7,8,9)

**About BRCA mutations**

BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce
proteins responsible for repairing damaged DNA and play an important role in 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 such as breast and ovarian cancer.^(10)

**About _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 65 countries, including those in the EU, for
the maintenance treatment of platinum-sensitive relapsed ovarian cancer, regardless
of BRCA status. It is approved in the US, the EU, Japan 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 44 countries, including
the US and Japan, for germline BRCA-mutated, HER2-negative, metastatic breast cancer,
previously treated with chemotherapy; in the EU, this includes locally advanced 
breast cancer. Regulatory reviews are underway in other jurisdictions for ovarian,
breast and pancreatic cancers.

_Lynparza_, which is being jointly developed and commercialised by AstraZeneca and
MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has
been used in over 25,000 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.

**About the AstraZeneca and MSD strategic oncology collaboration**

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD
outside the United States and Canada, announced a global strategic oncology collaboration
to co-develop and co-commercialise _Lynparza_, the world’s first PARP inhibitor,
and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types.
Working together, the companies will develop _Lynparza_ and selumetinib in combination
with other potential new medicines and as monotherapies. Independently, the companies
will develop _Lynparza_ and selumetinib in combination with their respective PD-
L1 and PD-1 medicines.

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