87.5% of patients treated with LYNPARZA were
alive at six years vs. 83.2% in the comparator arm
First and only PARP inhibitor to improve
survival in early breast cancer
Updated results from the OlympiA Phase III trial showed
AstraZeneca and Merck & Co., Inc’s, known as MSD outside of the
US and Canada, LYNPARZA® (olaparib) demonstrated sustained,
clinically meaningful improvements in overall survival (OS),
invasive disease-free survival (IDFS) and distant disease-free
survival (DDFS) at six years for patients with germline
BRCA-mutated (gBRCAm) HER2-negative high-risk early breast
cancer.
These results were presented today at the San Antonio Breast
Cancer Symposium 2024 (SABCS) (#GS1-09) and build on the positive
primary results published in The New England Journal of
Medicine.
At a median follow-up of 6.1 years in eligible patients, who had
completed local treatment and standard neoadjuvant or adjuvant
chemotherapy, results showed LYNPARZA reduced the risk of death by
28% (hazard ratio [HR] 0.72; 95% confidence interval [CI]
0.56-0.93) versus placebo. In addition, 87.5% of patients treated
with LYNPARZA remained alive versus 83.2% of those on placebo.
LYNPARZA also demonstrated sustained and clinically meaningful
improvements in the primary and secondary endpoints of IDFS and
DDFS. LYNPARZA reduced the risk of invasive breast cancer
recurrence, second cancers or death by 35% (HR 0.65; 95% CI;
0.53-0.78) and reduced the risk of distant disease recurrence or
death by 35% (HR 0.65; 95% CI; 0.53-0.81) versus placebo. The
benefit with LYNPARZA was consistent across all key subgroups,
including patients with high-risk, hormone-receptor-positive
disease.
Judy E. Garber, Chief of the Division of Cancer Genetics and
Prevention at Dana-Farber Cancer Institute and co-principal
investigator of the trial said: “These exciting long-term data from
OlympiA confirm that adjuvant treatment with olaparib for one year
continues to deliver clinically meaningful survival benefit for
patients with germline BRCA-mutated high-risk HER2-negative early
breast cancer even after six years, with benefit persisting in all
subgroups and with toxicity and pregnancy data reassuring for this
generally younger group. These data reinforce the importance of
germline BRCA testing at the time of diagnosis, so we can identify
all eligible patients who may benefit from treatment with olaparib
as early as possible.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “Two years ago, LYNPARZA became the first and
only PARP inhibitor to demonstrate a survival benefit in germline
BRCA-mutated, HER2-negative and high-risk early-stage breast
cancer. To see this benefit continue at six years of follow-up is
tremendous for patients and reinforces how LYNPARZA is continuing
to transform the treatment of BRCA-mutated early-stage breast
cancer.”
Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, Merck Research Laboratories,
said: “The durable long-term efficacy seen in the OlympiA study
reinforces LYNPARZA as an important treatment option for those
living with this truly challenging, very aggressive form of the
disease.”
Summary of results
LYNPARZA
(n=921)
Placebo
(n=915)
IDFS (primary endpoint)
HR (95% CI)
0.65 (0.53, 0.78)
IDFS rates at 6 years
79.6%
70.3%
DDFS (secondary endpoint)
HR (95% CI)
0.65 (0.53, 0.81)
DDFS rates at 6 years
83.5%
75.7%
OS (secondary endpoint)
HR (95% CI)
0.72 (0.56, 0.93)
OS rates at 6 years
87.5%
83.2%
The safety and tolerability profile of LYNPARZA in this trial
was in line with that observed in prior clinical trials and no new
safety signals were identified with longer follow-up. No evidence
of an increased risk of myelodysplastic syndrome or acute myeloid
leukemia was observed compared to those on placebo.
The OlympiA trial is coordinated by the Breast International
Group (BIG) in partnership with NRG Oncology, the US National
Cancer Institute (NCI), the Frontier Science & Technology
Research Foundation (FSTRF), AstraZeneca and Merck & Co.,
Inc.1
LYNPARZA is approved in the US, EU, Japan, and many other
countries for the treatment of gBRCAm, HER2-negative high-risk
early breast cancer. LYNPARZA is also approved in the US, EU,
Japan, and many other countries for the treatment of patients with
gBRCAm, HER2-negative metastatic breast cancer. In the EU, this
indication also includes patients with locally advanced breast
cancer.
IMPORTANT SAFETY INFORMATION ABOUT LYNPARZA® (olaparib)
tablets
CONTRAINDICATIONS There are no contraindications for
LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia
(MDS/AML): Occurred in approximately 1.2% of patients with
various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who
received LYNPARZA as a single agent or as part of a combination
regimen, consistent with the approved indications, and the majority
of events had a fatal outcome. The median duration of therapy in
patients who developed MDS/AML was approximately 2 years (range:
<6 months to >4 years). All of these patients had previous
chemotherapy with platinum agents and/or other DNA-damaging agents,
including radiotherapy.
In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian
cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who
received LYNPARZA and 0.8% (1/130) in patients who received placebo
based on an updated analysis. In PAOLA-1, of patients with newly
diagnosed advanced ovarian cancer with HRD-positive status, the
incidence of MDS/AML was 1.6% (4/255) in patients who received
LYNPARZA and 2.3% (3/131) in the control arm.
In SOLO-2, patients with BRCAm platinum-sensitive relapsed
ovarian cancer, the incidence of MDS/AML was 8% (15/195) in
patients who received LYNPARZA and 4% (4/99) in patients who
received placebo. The duration of LYNPARZA treatment prior to the
diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.
Do not start LYNPARZA until patients have recovered from
hematological toxicity caused by previous chemotherapy (≤Grade 1).
Monitor complete blood count for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities, interrupt LYNPARZA and monitor
blood count weekly until recovery.
If the levels have not recovered to Grade 1 or less after 4
weeks, refer the patient to a hematologist for further
investigations, including bone marrow analysis and blood sample for
cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.
Pneumonitis: Occurred in 0.8% of patients exposed to
LYNPARZA monotherapy, and some cases were fatal. If patients
present with new or worsening respiratory symptoms such as dyspnea,
cough, and fever, or a radiological abnormality occurs, interrupt
LYNPARZA treatment and initiate prompt investigation. Discontinue
LYNPARZA if pneumonitis is confirmed and treat patient
appropriately.
Venous Thromboembolism (VTE): Including severe or fatal
pulmonary embolism (PE) occurred in patients treated with LYNPARZA.
In the combined data of two randomized, placebo-controlled clinical
studies (PROfound and PROpel) in patients with metastatic
castration-resistant prostate cancer (N=1180), VTE occurred in 8%
of patients who received LYNPARZA, including pulmonary embolism in
6%. In the control arms, VTE occurred in 2.5%, including pulmonary
embolism in 1.5%. Monitor patients for signs and symptoms of venous
thrombosis and pulmonary embolism, and treat as medically
appropriate, which may include long-term anticoagulation as
clinically indicated.
Embryo-Fetal Toxicity: Based on its mechanism of action
and findings in animals, LYNPARZA can cause fetal harm. Verify
pregnancy status in females of reproductive potential prior to
initiating treatment.
Females Advise females of reproductive potential of the
potential risk to a fetus and to use effective contraception during
treatment and for 6 months following the last dose.
Males Advise male patients with female partners of reproductive
potential or who are pregnant to use effective contraception during
treatment and for 3 months following the last dose of LYNPARZA and
to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced
Ovarian Cancer Most common adverse reactions (Grades 1-4) in
≥10% of patients who received LYNPARZA in the first-line
maintenance setting for SOLO-1 were: nausea (77%),
fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%),
diarrhea (37%), constipation (28%), upper respiratory tract
infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia
(26%), decreased appetite (20%), dizziness (20%), neutropenia
(17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary
tract infection (13%), thrombocytopenia (11%), and stomatitis
(11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the first-line maintenance
setting for SOLO-1 were: decrease in hemoglobin (87%),
increase in mean corpuscular volume (87%), decrease in leukocytes
(70%), decrease in lymphocytes (67%), decrease in absolute
neutrophil count (51%), decrease in platelets (35%), and increase
in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian
Cancer in Combination with Bevacizumab Most common adverse
reactions (Grades 1-4) in ≥10% of patients treated with
LYNPARZA/bevacizumab and at a ≥5% frequency compared to
placebo/bevacizumab in the first-line maintenance setting
for PAOLA-1 were: nausea (53%), fatigue (including asthenia)
(53%), anemia (41%), lymphopenia (24%), vomiting (22%), and
leukopenia (18%).
In addition, the most common adverse reactions (≥10%) for
patients receiving LYNPARZA/bevacizumab irrespective of the
frequency compared with the placebo/bevacizumab arm were: diarrhea
(18%), neutropenia (18%), urinary tract infection (15%), and
headache (14%).
In addition, venous thromboembolism occurred more commonly in
patients receiving LYNPARZA/bevacizumab (5%) than in those
receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients for LYNPARZA in combination with bevacizumab in the
first-line maintenance setting for PAOLA-1 were:
decrease in hemoglobin (79%), decrease in lymphocytes (63%),
increase in serum creatinine (61%), decrease in leukocytes (59%),
decrease in absolute neutrophil count (35%), and decrease in
platelets (35%).
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian
Cancer Most common adverse reactions (Grades 1-4) in ≥20% of
patients who received LYNPARZA in the maintenance setting
for SOLO-2 were: nausea (76%), fatigue (including asthenia)
(66%), anemia (44%), vomiting (37%), nasopharyngitis/upper
respiratory tract infection (URI)/influenza (36%), diarrhea (33%),
arthralgia/myalgia (30%), dysgeusia (27%), headache (26%),
decreased appetite (22%), and stomatitis (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the maintenance setting
for SOLO-2 were: increase in mean corpuscular volume (89%),
decrease in hemoglobin (83%), decrease in leukocytes (69%),
decrease in lymphocytes (67%), decrease in absolute neutrophil
count (51%), increase in serum creatinine (44%), and decrease in
platelets (42%).
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm,
HER2-Negative, High-Risk Early Breast Cancer Most common
adverse reactions (Grades 1-4) in ≥10% of patients who received
LYNPARZA in the adjuvant setting for OlympiA were:
nausea (57%), fatigue (including asthenia) (42%), anemia (24%),
vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%),
neutropenia (16%), decreased appetite (13%), dysgeusia (12%),
dizziness (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the adjuvant setting for
OlympiA were: decrease in lymphocytes (77%), increase in
mean corpuscular volume (67%), decrease in hemoglobin (65%),
decrease in leukocytes (64%), and decrease in absolute neutrophil
count (39%).
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast
Cancer Most common adverse reactions (Grades 1-4) in ≥20% of
patients who received LYNPARZA in the metastatic setting for
OlympiAD were: nausea (58%), anemia (40%), fatigue
(including asthenia) (37%), vomiting (30%), neutropenia (27%),
respiratory tract infection (27%), leukopenia (25%), diarrhea
(21%), and headache (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the metastatic setting for
OlympiAD were: decrease in hemoglobin (82%), decrease in
lymphocytes (73%), decrease in leukocytes (71%), increase in mean
corpuscular volume (71%), decrease in absolute neutrophil count
(46%), and decrease in platelets (33%).
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic
Pancreatic Adenocarcinoma Most common adverse reactions (Grades
1-4) in ≥10% of patients who received LYNPARZA in the first-line
maintenance setting for POLO were: fatigue (60%), nausea
(45%), abdominal pain (34%), diarrhea (29%), anemia (27%),
decreased appetite (25%), constipation (23%), vomiting (20%), back
pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%),
dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia
(11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the first-line maintenance
setting for POLO were: increase in serum creatinine
(99%), decrease in hemoglobin (86%), increase in mean corpuscular
volume (71%), decrease in lymphocytes (61%), decrease in platelets
(56%), decrease in leukocytes (50%), and decrease in absolute
neutrophil count (25%).
ADVERSE REACTIONS—HRR Gene-mutated Metastatic
Castration-Resistant Prostate Cancer Most common adverse
reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA
for PROfound were: anemia (46%), fatigue (including
asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea
(21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and
dyspnea (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA for PROfound were: decrease
in hemoglobin (98%), decrease in lymphocytes (62%), decrease in
leukocytes (53%), and decrease in absolute neutrophil count
(34%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate
Cancer in Combination with Abiraterone and Prednisone or
Prednisolone Most common adverse reactions (Grades 1-4) in ≥10%
of patients who received LYNPARZA/abiraterone with a difference of
≥5% compared to placebo for PROpel were: anemia (48%),
fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%),
decreased appetite (16%), lymphopenia (14%), dizziness (14%), and
abdominal pain (13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of
patients who received LYNPARZA/abiraterone for PROpel were:
decrease in hemoglobin (97%), decrease in lymphocytes (70%),
decrease in platelets (23%), and decrease in absolute neutrophil
count (23%).
DRUG INTERACTIONS Anticancer Agents: Clinical
studies of LYNPARZA with other myelosuppressive anticancer agents,
including DNA-damaging agents, indicate a potentiation and
prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or
moderate CYP3A inhibitors when using LYNPARZA. If a strong or
moderate CYP3A inhibitor must be coadministered, reduce the dose of
LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice,
Seville oranges, and Seville orange juice during LYNPARZA
treatment.
CYP3A Inducers: Avoid coadministration of strong or
moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS Lactation: No data are
available regarding the presence of olaparib in human milk, its
effects on the breastfed infant or on milk production. Because of
the potential for serious adverse reactions in the breastfed
infant, advise a lactating woman not to breastfeed during treatment
with LYNPARZA and for 1 month after receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have
not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild or moderate hepatic impairment
(Child-Pugh classification A and B). There are no data in patients
with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended
in patients with mild renal impairment (CLcr 51-80 mL/min estimated
by Cockcroft-Gault). In patients with moderate renal impairment
(CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice
daily. There are no data in patients with severe renal impairment
or end-stage renal disease (CLcr ≤30 mL/min).
INDICATIONS LYNPARZA is a poly (ADP-ribose) polymerase
(PARP) inhibitor indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer For
the maintenance treatment of adult patients with deleterious or
suspected deleterious germline or somatic BRCA-mutated (gBRCAm or
sBRCAm) advanced epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in complete or partial response to
first-line platinum-based chemotherapy. Select patients for therapy
based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer
in Combination with Bevacizumab In combination with bevacizumab
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 first-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
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.
Maintenance BRCA-mutated Recurrent Ovarian Cancer For the
maintenance treatment of adult patients with deleterious or
suspected deleterious germline or somatic BRCA-mutated (gBRCAm or
sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary
peritoneal cancer, who are in complete or partial response to
platinum-based chemotherapy. Select patients for therapy based on
an FDA-approved companion diagnostic for LYNPARZA.
Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early
Breast Cancer For the adjuvant treatment of adult patients with
deleterious or suspected deleterious gBRCAm, human epidermal growth
factor receptor 2 (HER2)-negative, high-risk early breast cancer
who have been treated with neoadjuvant or adjuvant chemotherapy.
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer For the
treatment of adult patients with deleterious or suspected
deleterious gBRCAm, human epidermal growth factor receptor 2
(HER2)-negative metastatic breast cancer who have been treated with
chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
Patients with hormone receptor (HR)-positive breast cancer should
have been treated with a prior endocrine therapy or be considered
inappropriate for endocrine therapy. Select patients for therapy
based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance gBRCAm Metastatic Pancreatic
Cancer For the maintenance treatment of adult patients with
deleterious or suspected deleterious gBRCAm metastatic pancreatic
adenocarcinoma whose disease has not progressed on at least 16
weeks of a first-line platinum-based chemotherapy regimen. Select
patients for therapy based on an FDA-approved companion diagnostic
for LYNPARZA.
HRR Gene-mutated Metastatic Castration-Resistant Prostate
Cancer For the treatment of adult patients with deleterious or
suspected deleterious germline or somatic homologous recombination
repair (HRR) gene-mutated metastatic castration-resistant prostate
cancer (mCRPC) who have progressed following prior treatment with
enzalutamide or abiraterone. Select patients for therapy based on
an FDA-approved companion diagnostic for LYNPARZA.
BRCAm Metastatic Castration-Resistant Prostate Cancer in
Combination with Abiraterone and Prednisone or Prednisolone In
combination with abiraterone and prednisone or prednisolone
(abi/pred) for the treatment of adult patients with deleterious or
suspected deleterious BRCA-mutated (BRCAm) metastatic
castration-resistant prostate cancer (mCRPC). Select patients for
therapy based on an FDA-approved companion diagnostic for
LYNPARZA.
Notes
Early breast cancer Early breast cancer is defined as
cancer confined to the breast with or without regional lymph node
involvement, and the absence of distant metastatic disease.2 In the
US, the 5-year survival rate is 99.6% for localized breast cancer
(only found in the breast area) and 86.7% for regional breast
cancer (cancer that has spread outside the breast to nearby
structures or lymph nodes).3 Despite advancements in the treatment
of early breast cancer, up to 30% of patients with high-risk
clinical and/or pathologic features recur within the first few
years and patients with gBRCA mutations are more likely to be
diagnosed at a younger age than those without these
mutations.4,5
Breast cancer is one of the most biologically diverse tumor
types with various factors fueling its development and
progression.6 The discovery of biomarkers in the development of
breast cancer has greatly impacted scientific understanding of the
disease.7
OlympiA OlympiA is a phase III, double-blind, parallel
group, placebo-controlled, multicenter trial evaluating the
efficacy and safety of LYNPARZA tablets versus placebo as a
12-month adjuvant treatment for adult patients with gBRCAm
HER2-negative early breast cancer, who have completed neoadjuvant
or adjuvant chemotherapy.1 The primary endpoint of the trial is
invasive disease-free survival defined as time from randomization
to date of first loco-regional or distant recurrence or new cancer
or death from any cause. Key secondary endpoints include distant
disease-free survival and overall survival, which is defined as
time from randomization until documented evidence of first distant
recurrence of breast cancer or death without distant
recurrence.1
Breast International Group (BIG) BIG is an international
not-for-profit organization for academic breast cancer research
groups from around the world, based in Brussels, Belgium.
Founded by leading European opinion leaders in 1999, the
organization aims to address fragmentation in breast cancer
research and now represents a network of over 50 like-minded
research groups affiliated with specialized hospitals, research
centers 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 programs.
Frontier Science & Technology Research Foundation
(FSTRF) FSTRF is a non-profit, research organization 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 centers 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.
BRCA 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.8 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/tumors harboring a deficiency in homologous
recombination-related (HRR) genes, such as those with mutations in
BRCA1 and/or BRCA2, or those where deficiency is induced by other
agents (such as new hormonal agents [NHAs]).
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 may also help enhance immunogenicity
and increase the impact of anti-tumor immune responses.
LYNPARZA is currently approved in a number of countries across
multiple tumor 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 homologous recombination
repair deficient (HRD)-positive advanced ovarian cancer,
respectively; for gBRCAm metastatic pancreatic cancer; in
combination with abiraterone for the treatment of metastatic
castration-resistant prostate cancer (mCRPC) when chemotherapy is
not clinically indicated (EU only) and for BRCAm mCRPC (US and
Japan); as monotherapy for HRR gene-mutated mCRPC in patients who
have progressed on prior NHA treatment (BRCAm only in the EU and
Japan); and in combination with durvalumab following durvalumab
plus chemotherapy as 1st-line treatment for advanced or recurrent
endometrial cancer that is mismatch repair proficient (EU and
Japan). In China, LYNPARZA is approved for the treatment of
BRCA-mutated mCRPC as well as 1st-line maintenance treatment with
bevacizumab for HRD-positive advanced ovarian cancer.
LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck & Co., Inc., known as MSD outside the US
and Canada, has been used to treat over 140,000 patients worldwide.
LYNPARZA has a broad clinical trial development program, and
AstraZeneca and Merck & Co., Inc., are working together to
understand how it may affect multiple PARP-dependent tumors 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 Merck & Co., Inc., 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-commercialize LYNPARZA, the world’s first PARP inhibitor,
and selumetinib, a mitogen-activated protein kinase (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. The companies will develop LYNPARZA and
selumetinib in combination with their respective PD-L1 and PD-1
medicines independently.
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 catalyze 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 is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialization of prescription medicines in
Oncology, Rare Diseases and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
125 countries, and its innovative medicines are used by millions of
patients worldwide. For more information, please visit
www.astrazeneca-us.com and follow us on social media
@AstraZeneca.
References
- ClinicalTrials.gov. Olaparib as Adjuvant Treatment in Patients
with Germline BRCA Mutated High Risk HER2 Negative Primary Breast
Cancer (OlympiA). Available at:
https://clinicaltrials.gov/ct2/show/NCT02032823. Accessed December
2024.
- National Cancer Institute. Early-stage breast cancer. Available
at:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer.
Accessed December 2024.
- National Cancer Institute: Surveillance, Epidemiology, and End
Results Program. Cancer Stat Facts: Female Breast Cancer. Available
at: https://seer.cancer.gov/statfacts/html/breast.html. Accessed
December 2024.
- O'Shaughnessy J, et al. Prevalence of germline BRCA mutations
in HER2-negative metastatic breast cancer: global results from the
real-world, observational BREAKOUT study. Breast Cancer Research.
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US-96561 Last Updated 12/24
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