LYNPARZA™ (olaparib) Phase III SOLO-2 Data Demonstrated Progression-Free Survival Benefit in BRCA-Mutated Ovarian Cancer as Maintenance Therapy

LYNPARZA reduced risk of disease progression by 70% with an
investigator-assessed progression-free survival of 19.1 vs 5.5 months
with placebo

Blinded independent central review showed significant
progression-free survival of 30.2 months vs 5.5 months with placebo

LYNPARZA tablets demonstrated a safety profile generally
consistent with previous studies

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today presented results from the Phase III SOLO-2 trial
demonstrating a significant improvement in progression-free survival
(PFS) in germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed
ovarian cancer patients treated with LYNPARZA™ (olaparib) tablets
(300mg twice daily), compared with placebo in the maintenance setting.
The trial met its primary endpoint of investigator-assessed PFS (HR
0.30; 95% CI 0.22-0.41; P<0.0001; median 19.1 months vs 5.5 months).1

PFS as measured by Blinded Independent Central Review (BICR) evaluation,
a pre-specified sensitivity analysis supporting the primary endpoint,
demonstrated a median PFS of 30.2 months vs 5.5 months for placebo,
representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35;
P<0.0001).1

Additionally, a statistically-significant benefit in time to second
progression or death (PFS2) was also seen in patients treated with
LYNPARZA (HR 0.50; 95% CI 0.34-0.72; P=0.0002; median not reached vs
18.4 months), compared with placebo, as well as improvements in other
key secondary endpoints.1

 

Table 1. Progression-Free Survival by investigator and BICR
assessment:

         
Analysis  

Median
progression-free
survival, months

  Hazard ratio

Investigator-
assessed
analysis

  LYNPARZA   19.1   0.30 (95% CI, 0.22-0.41), P<0.0001
  Placebo   5.5  

Blinded
Independent
Central Review

LYNPARZA   30.2 0.25 (95% CI, 0.18-0.35), P<0.0001
  Placebo   5.5  
 

These results, presented at the Society of Gynecologic Oncology Annual
Meeting on Women’s Cancer in National Harbor, Maryland, build upon prior
data in this setting, demonstrating the potential of LYNPARZA as a
maintenance therapy in relapsed ovarian cancer.1,2

Richard Penson, MD, Associate Professor of Medicine at Harvard Medical
School and Clinical Director of Medical Gynecologic Oncology at
Massachusetts General Hospital said: “The SOLO-2 data demonstrated a
statistically significant and clinically meaningful improvement in
outcomes for those who took olaparib. The results, which showed a delay
in disease progression in the maintenance setting, highlight the impact
of PARP inhibition at the forefront of the important advances we are
making in targeting ovarian cancer.”

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: “We are extremely pleased
with the results from SOLO-2, which support the potential benefit of
LYNPARZA tablets as a maintenance therapy for patients with relapsed
ovarian cancer. The tablet formulation may offer patients a reduced pill
burden for LYNPARZA and a safety profile that is generally consistent
with previous trials. We will work with regulatory authorities to make
LYNPARZA tablets available to patients as quickly as possible.”

The safety profile for patients treated with LYNPARZA tablets during the
trial was generally consistent to those observed with the
currently-approved capsule formulation.1 Any adverse events
(AE) Grade ≥3 were reported in 36.9% of patients treated with LYNPARZA
and in 18.2% of patients who received placebo.1 The most
common non-hematological AEs reported at a frequency of ≥20% in the
LYNPARZA arm versus placebo were nausea (75.9% vs 33.3%),
fatigue/asthenia (65.6% vs 39.4%), and vomiting (37.4% vs 19.2%).1
Grade ≥3 non-hematological AEs reported at a frequency of ≥2.5% in the
LYNPARZA arm versus placebo were fatigue/asthenia (4.1% vs 2.0%),
vomiting (2.6 % vs 1.0%), abdominal pain (2.6% vs 3.0%), nausea (2.6% vs
0.0%), diarrhea (1.0% vs 0.0%), and constipation (0.0% vs 3.0%).1

The most common hematological AEs reported in the LYNPARZA arm versus
placebo were anemia (43.6% vs 8.1%), neutropenia (19.5% vs 6.1%), and
thrombocytopenia (13.8% vs 3.0%).1 Grade ≥3 hematological AEs
reported in the LYNPARZA arm versus placebo were anemia (19.5% vs 2.0%),
neutropenia (5.1% vs 4.0%), and thrombocytopenia (1.0% vs 1.0%).1

The 300mg twice-daily tablet dose potentially reduces the pill burden
for patients from 16 capsules to four tablets per day.

LYNPARZA tablets are an investigational formulation and are not
FDA-approved for any use.3,4 LYNPARZA capsules (400mg twice
daily) are currently approved in the U.S. 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.3

IMPORTANT SAFETY INFORMATION

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 (≤Grade 1). For
prolonged hematological toxicities, interrupt LYNPARZA and monitor blood
counts weekly until recovery. If the levels have not recovered to Grade
1 or less after four 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. A pregnancy
test should be performed on all pre-menopausal women prior to treatment.
Advise females of reproductive potential of the potential risk to a
fetus and to use effective contraception during treatment and for six
months after receiving the final dose.

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 decrease in hemoglobin (90%),
decrease in absolute neutrophil count (32%), decrease in platelets
(30%), decrease in lymphocytes (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

Lactation: No data are available regarding the presence of
olaparib in human milk, the 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 one month after receiving the final dose.

Hepatic Impairment: No dose adjustment is required in patients
with mild hepatic impairment (Child-Pugh classification A). There are no
data in patients with moderate or severe hepatic impairment.

Renal Impairment: No dosage adjustment is necessary in 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 300mg
twice daily. There are no data in patients with severe renal impairment
or end-stage renal disease (CLcr ≤30 mL/min).

Please see complete
Prescribing Information, including Patient Information (Medication
Guide).

NOTES TO EDITORS

About SOLO-2

SOLO-2 was a Phase III, randomized, double-blind, multicenter trial
designed to determine the efficacy of LYNPARZA tablets as a maintenance
monotherapy compared with placebo, in patients with platinum-sensitive
relapsed or recurrent gBRCA-mutated ovarian cancer. 4 The
trial, conducted in collaboration with the European Network for
Gynaecological Oncological Trial Groups (ENGOT) and Groupe
d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du
sein (GINECO), randomized 295 patients with documented germline BRCA1 or
BRCA2 mutations who had received at least two prior lines of
platinum-based chemotherapy and were in complete or partial response.4,5
Eligible patients were randomized to receive either LYNPARZA tablets
(300mg twice daily) or placebo.4

About AstraZeneca in Ovarian Cancer

In the U.S., ovarian cancer is the ninth most commonly diagnosed cancer
and the fifth most common cause of cancer death in women.6
The risk of developing ovarian cancer is increased in women with
specific inherited genetic abnormalities, including BRCA mutations.7
AstraZeneca is committed to the continued development of our R&D
portfolio for ovarian cancer, with a focus on improved care for all
patients.

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.3

LYNPARZA is the foundation of AstraZeneca’s industry-leading portfolio
of compounds targeting DDR mechanisms in cancer cells.8-10

LYNPARZA tablets are currently being investigated in monotherapy and in
combinations in a range of tumor types including breast, prostate, and
pancreatic cancer.11-14 LYNPARZA tablets are an
investigational formulation and are not FDA-approved for any use.3

About ENGOT

ENGOT (European Network for Gynaecological Oncological Trial groups) is
a research network of the European Society of Gynaecological Oncology
(ESGO) and was founded in 2007. Currently, ENGOT consists of 19
cooperative groups from 15 European countries. ENGOT’s ultimate goal is
to bring the best treatment to gynecological cancer patients through the
best science, and enabling every patient in every European country to
access a clinical trial. ENGOT coordinates and promotes multinational
clinical trials within Europe on patients with gynecological cancer.
This coordination is particularly relevant for academic clinical trials,
translational research, research on rare diseases, and for clinical
trials sponsored by the industry.15

About GINECO

GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de
l’Ovaire et du sein) is the French Cooperative Group in Oncology labeled
by INCA (Institut National du Cancer or French NCI) for developing and
conducting gynecological and advanced breast cancer clinical trials at
the national and international level. The network is nationwide over 500
specialized investigators belonging to more than 150 public or private
oncology units. The GINECO group was founded in 1993 and is member of
international consortia such as ENGOT and GCIG (Gynecologic Cancer
InterGroup). GINECO was the ENGOT leading group for SOLO-2 trial.4,5

About 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 at least six new
medicines to be launched between 2014 and 2020 and a broad pipeline of
small molecules and biologics in development, we are committed to
advance New 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

  1. Pujade-Lauraine E., Ledermann J., Penson R., et al., Treatment with
    olaparib monotherapy in the maintenance setting significantly improves
    progression-free survival in patients with platinum-sensitive relapsed
    ovarian cancer: Results from the Phase III SOLO-2 Study. Presented at
    the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer
    (SGO), March 12 – 15. National Harbor, Maryland.
  2. Ledermann J., Harter P., Gourley M., et al., Olaparib Maintenance
    Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. N Engl J Med
    2012;366:1382-92.
  3. LYNPARZA (olaparib) Prescribing Information. AstraZeneca
    Pharmaceuticals LP, Wilmington, DE.
  4. National Institutes of Health. Olaparib Treatment in BRCA Mutated
    Ovarian Cancer Patients After Complete or Partial Response to Platinum
    Chemotherapy. Available
    Online
    . Accessed March 2017.
  5. GINECO. Presentation of GINECO. Association ARCAGY – GINECO – Hotel
    Dieu Hospital. Available
    Online
    . Accessed March 2017.
  6. Centers for Disease Control and Prevention. Ovarian Cancer Statistics. Available
    Online
    . Last Updated June 21, 2016. Accessed March 2017.
  7. National Cancer Institute. BRCA1 and BRCA2: cancer risk and genetic
    testing. Available
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  8. Food and Drug Administration. FDA approves Lynparza to treat advanced
    ovarian cancer. Available
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  9. O’Connor M. ‘Targeting The DNA Damage Response In Cancer’ (2015) Mol
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  10. 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
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  11. National Institutes of Health. Olaparib as Adjuvant Treatment in
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    Breast Cancer (OlympiA). Available
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    . Accessed March 2017.
  12. 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
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  13. National Institutes of Health. Olaparib in gBRCA Mutated Pancreatic
    Cancer Whose Disease Has Not Progressed on First Line Platinum-Based
    Chemotherapy (POLO). Available
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  14. National Institutes of Health. Ph II Study to Evaluate Olaparib With
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  15. European Network of Gynaecological Oncological Trial Groups. Mission
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    Oncology 2016. Available
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©2017 AstraZeneca. All rights reserved.

3323614 Last Updated 3/17

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