LYNPARZA provided a
statistically-significant improvement in progression-free survival
compared to chemotherapy
First positive randomized trial to evaluate
the efficacy and safety of a PARP inhibitor beyond ovarian
cancer
AstraZeneca today announced positive results from its Phase III
OlympiAD trial comparing LYNPARZA™ (olaparib) tablets (300mg twice
daily) to physician’s choice of a standard of care chemotherapy in
the treatment of patients with HER2-negative metastatic breast
cancer harboring germline BRCA1 or BRCA2 mutations.1 Patients
treated with LYNPARZA showed a statistically-significant and
clinically-meaningful improvement in progression-free survival
(PFS) compared with those who received chemotherapy (capecitabine,
vinorelbine or eribulin).
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said: “These
results are positive news for patients with BRCA-mutated metastatic
breast cancer, a disease with a high unmet need, and are the first
positive Phase III data for a PARP inhibitor beyond ovarian cancer.
This is highly encouraging for the development of our broad
portfolio which aims to treat multiple cancers by targeting DNA
damage response pathways.”
Initial findings from the OlympiAD study indicate that the
safety profile of LYNPARZA was consistent with previous
studies.
A full evaluation of the OlympiAD data is ongoing and the
results will be submitted for presentation at a forthcoming medical
meeting. AstraZeneca will be working with regulatory authorities to
make LYNPARZA available to patients with this type of breast
cancer.
LYNPARZA tablets are an investigational formulation and are not
FDA-approved for any use.1,2 LYNPARZA capsules (400mg twice daily)
are currently approved in the US as a monotherapy in patients with
deleterious or suspected deleterious germline BRCA-mutated (as
detected by an FDA-approved test) advanced ovarian cancer who have
been treated with three or more prior lines of chemotherapy. The
indication is approved under accelerated approval based on
objective response rate and duration of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.2
Important Safety Information About LYNPARZA™
(olaparib)
WARNINGS AND PRECAUTIONS
There are no contraindications for LYNPARZA.
Myelodysplastic Syndrome/Acute Myeloid Leukemia
(MDS/AML): Occurred in <1% of patients treated with
LYNPARZA, and the majority of those reports were fatal. The
duration of therapy in patients who developed secondary MDS/AML
varied from <6 months to >2 years. In a randomized
placebo-controlled trial, MDS/AML occurred in 2% of patients
treated with LYNPARZA. All of these patients had previous
chemotherapy with platinum agents and/or other DNA damaging agents,
including radiotherapy, and some of these patients also had a
history of previous cancer or of bone marrow dysplasia.
Monitor patients for hematological toxicity at baseline and
monthly thereafter. Do not start LYNPARZA until patients have
recovered from hematological toxicity caused by previous
chemotherapy (≤CTCAE Grade 1). For prolonged hematological
toxicities, interrupt LYNPARZA and monitor blood counts weekly
until recovery. If the levels have not recovered to CTCAE 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 if MDS/AML is confirmed.
Pneumonitis: Occurred in <1% of patients exposed to
LYNPARZA, and some cases were fatal. If patients present with new
or worsening respiratory symptoms such as dyspnea, fever, cough,
wheezing, or a radiological abnormality occurs, interrupt treatment
with LYNPARZA and initiate prompt investigation. Discontinue if
pneumonitis is confirmed.
Embryo-Fetal Toxicity: LYNPARZA can cause fetal harm.
Advise females of reproductive potential of the potential risk to a
fetus and to avoid pregnancy by using effective contraception
during treatment and for at least one month after receiving the
last dose of LYNPARZA.
ADVERSE REACTIONS
In clinical studies, the most common adverse reactions (Grades
1-4) in ≥20% of patients included anemia (34%), nausea (75%),
fatigue (including asthenia) (68%), vomiting (43%), diarrhea (31%),
dysgeusia (21%), dyspepsia (25%), headache (25%), decreased
appetite (25%), nasopharyngitis/pharyngitis/URI (43%), cough (21%),
arthralgia/musculoskeletal pain (32%), myalgia (25%), back pain
(25%), dermatitis/rash (25%), and abdominal pain/discomfort
(47%).
Common lab abnormalities (Grades 1-4) included anemia (90%),
neutropenia (32%), thrombocytopenia (30%), lymphopenia (56%), mean
corpuscular volume elevation (85%), and increase in creatinine
(30%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA in
combination with other myelosuppressive anticancer agents,
including DNA damaging agents, indicate a potentiation and
prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid concomitant use of strong and
moderate CYP3A inhibitors. If the strong or moderate CYP3A
inhibitor must be co-administered, reduce the dose of LYNPARZA.
Advise patients to avoid grapefruit and Seville oranges during
LYNPARZA treatment.
CYP3A Inducers: Avoid concomitant use of strong and
moderate CYP3A inducers when using LYNPARZA. If a moderate inducer
cannot be avoided, be aware of a potential for decreased efficacy
of LYNPARZA.
USE IN SPECIFIC POPULATIONS
Nursing Mothers: Because many drugs are excreted in human
milk and because of the potential for serious adverse reactions in
nursing infants from LYNPARZA, a decision should be made whether to
discontinue nursing or to discontinue the drug, taking into account
the importance of the drug to the mother.
Renal Impairment: No dosage adjustment is necessary for
patients with mild renal impairment (CLcr 51-80 mL/min). In
patients with moderate renal impairment (CLcr 31-50 mL/min), reduce
the dose to 300 mg twice daily. There are no data in patients with
severe renal impairment or end-stage renal disease (CLcr ≤30
mL/min).
Hepatic Impairment: There are no data in patients with
baseline hepatic impairment (serum bilirubin >1.5 times upper
limit of normal).
Please see complete Prescribing Information, including
Patient Information (Medication Guide).
NOTES TO EDITORS
About Metastatic Breast Cancer
Approximately one in eight women are diagnosed with breast
cancer in the United States.3 Of these patients, approximately
one-third are either diagnosed with or progress to the metastatic
stage of the disease.4 Despite treatment options increasing during
the past three decades, there is currently no cure for patients
diagnosed with metastatic breast cancer.5,6 Thus, the primary aim
of treatment is to slow progression of the disease for as long as
possible, improving or at least maintaining, a patient’s quality of
life.4
About OlympiAD
OlympiAD is a randomized, multi-center Phase III trial assessing
the efficacy and safety of LYNPARZA (300mg twice daily) to
‘physician’s choice’ chemotherapy (capecitabine, vinorelbine,
eribulin) in 302 patients with HER2-negative metastatic breast
cancer with germline BRCA1 or BRCA2 mutations, which are predicted
or suspected to be deleterious. The international study was
conducted in 19 countries from across Europe, Asia, North America
and South America.1
The primary endpoint of the trial was progression-free survival
(PFS) as measured by a Blinded Independent Central Review (BICR).
Secondary endpoints include overall survival (OS), time to second
progression or death (PFS2), objective response rate (ORR), and
effect on health-related quality of life (HRQoL).1
About Germline BRCA Mutations
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. As a result, cells are more likely to develop
additional genetic alterations that can lead to cancer.7
Specific inherited mutations in BRCA1 and BRCA2 increase the
risk of female breast and ovarian cancers, and they have been
associated with increased risks of several additional types of
cancer. Together, BRCA1 and BRCA2 mutations account for about 20 to
25 percent of hereditary breast cancers and about 5 to 10 percent
of all breast cancers. In addition, mutations in BRCA1 and BRCA2
account for around 15 percent of ovarian cancers overall. Breast
and ovarian cancers associated with BRCA1 and BRCA2 mutations tend
to develop at younger ages than their nonhereditary
counterparts.7
About LYNPARZATM (olaparib)
LYNPARZATM (olaparib) was the first FDA-approved oral poly
ADP-ribose polymerase (PARP) inhibitor that may exploit tumor DNA
damage response (DDR) pathway deficiencies to preferentially kill
cancer cells.8-10 Specifically, in vitro studies have shown that
olaparib-induced cytotoxicity may involve inhibition of PARP
enzymatic activity and increased formation of PARP-DNA complex,
resulting in disruption of cellular homeostasis and cell death.2
LYNPARZA is the foundation of AstraZeneca’s industry-leading
portfolio of compounds targeting DNA damage response (DDR)
mechanisms in cancer cells.8-10
LYNPARZATM is currently being investigated in another separate
non-metastatic breast cancer Phase III study called OlympiA.11
LYNPARZA tablets are currently being investigated in monotherapy
and in combinations in a range of tumor types including ovarian,
prostate, and pancreatic cancer.12-15 LYNPARZA tablets are an
investigational formulation and are not FDA-approved for any
use.1,10
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly growing portfolio of new medicines that have the potential
to transform patients’ lives and the Company’s future. With at
least 6 new medicines to be launched between 2014 and 2020 and a
broad pipeline of small molecules and biologics in development, we
are committed to advancing Oncology as one of AstraZeneca’s six
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our investment in
Acerta Pharma in hematology.
By harnessing the power of four scientific platforms --
immuno-oncology, the genetic drivers of cancer and resistance, DNA
damage response and antibody drug conjugates -- and by
championing the development of personalized combinations,
AstraZeneca has the vision to redefine cancer treatment and one day
eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas - Oncology, Cardiovascular & Metabolic
Diseases and Respiratory. The Company also is selectively active in
the areas of autoimmunity, neuroscience and infection. AstraZeneca
operates in over 100 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 Twitter
@AstraZenecaUS.
References
- National Institutes of Health.
Assessment of the Efficacy and Safety of Olaparib Monotherapy
Versus Physicians Choice Chemotherapy in the Treatment of
Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations
(OlympiAD). Available Online. Accessed February 2017.
- LYNPARZA (olaparib) Prescribing
Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- National Cancer Institute. SEER Cancer
Stat Facts: Female Breast Cancer. Available Online. Accessed
February 2017.
- O’Shaughnessy J. Extending Survival
with Chemotherapy in Metastatic Breast Cancer. The Oncologist
2005;10(3):20–29.
- American Cancer Society. Breast Cancer
Facts & Figures 2015-2016. Available Online. Accessed February
2017.
- American Cancer Society. Managing
Cancer as a Chronic Illness. Available Online. Accessed February
2017.
- National Cancer Institute. BRCA1 and
BRCA2: Cancer Risk and Genetic Testing. Available Online. Accessed
February 2017.
- Food and Drug Administration. FDA
approves Lynparza to treat advanced ovarian cancer. Available
Online. Accessed February 2017.
- O’Connor M. ‘Targeting The DNA Damage
Response In Cancer’ (2015) Mol Cell.60.547-560. Accessed February
2017.
- Tutt A N J, Lord C J, McCabe N.
Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design
of New Therapeutic Strategies for Cancer. Cold Spring Harb
Symp Quant Niol. 2005;70:139-48.
- National Institutes of Health. Olaparib
as Adjuvant Treatment in Patients With Germline BRCA Mutated High
Risk HER2 Negative Primary Breast Cancer (OlympiA). Available
Online. Accessed February 2017.
- National Institutes of Health. Olaparib
Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following
First Line Platinum Based Chemotherapy (SOLO-1). Available Online.
Accessed February 2017.
- National Institutes of Health. Olaparib
Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or
Partial Response to Platinum Chemotherapy. Available Online.
Accessed February 2017.
- National Institutes of Health. Olaparib
in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed
on First Line Platinum-Based Chemotherapy (POLO). Available Online.
Accessed February 2017.
- National Institutes of Health. Ph II
Study to Evaluate Olaparib With Abiraterone in Treating Metastatic
Castration Resistant Prostate Cancer. Available Online. Accessed
February 2017.
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AstraZenecaMedia InquiriesMichele Meixell, +1
302-885-2677Abigail Bozarth, +1 302-885-2677
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