Landmark 5-year follow-up of PAOLA-1 Phase
III trial demonstrated LYNPARZA plus bevacizumab meaningfully
extended survival with 65.5% of HRD-positive patients surviving 5
years vs. 48.4% treated with bevacizumab and placebo
SOLO-1 Phase III trial demonstrated 67% of
advanced ovarian cancer patients with BRCA mutations treated with
LYNPARZA were alive at 7 years vs. 47% on placebo
Positive long-term follow-up results from the PAOLA-1 and SOLO-1
Phase III trials of LYNPARZA® (olaparib), jointly developed and
commercialized by AstraZeneca and Merck & Co., Inc., known as
MSD outside the US and Canada, with or without bevacizumab
demonstrated clinically meaningful improvements in overall survival
(OS). Further results showed class-leading progression-free
survival (PFS) in combination with bevacizumab for homologous
recombination deficiency (HRD)-positive patients, versus active
comparator, bevacizumab, and as monotherapy for patients with BRCA
mutations, versus placebo, respectively.
Both trials which were conducted in biomarker-selected, newly
diagnosed patients with advanced ovarian cancer in the 1st-line
maintenance setting also demonstrated a consistent safety
profile.1,2
The results for PAOLA-1 (Abstract #LBA29) and SOLO-1 (Abstract
#517O) were presented on September 9 at the 2022 European Society
of Medical Oncology (ESMO) and SOLO-1 results were published in
Journal of Clinical Oncology.
Ovarian cancer is one of the most common gynecologic cancers,
with a poor prognosis and a high mortality rate.3 Over two thirds
of patients are diagnosed with advanced disease, and approximately
50-70% of these patients die within five years.4,5 Up to one in
five women with advanced ovarian cancer have a BRCA mutation, and
roughly half of women have HRD-positive tumors (which includes
those with a BRCA mutation).6-8
Professor Isabelle Ray-Coquard, principal investigator from the
PAOLA-1 trial and the President of the Gineco group, said: “For
women facing an advanced ovarian cancer diagnosis who are
HRD-positive, a targeted treatment in the 1st-line maintenance
setting is critical to helping them live longer. These latest
results at the five-year landmark demonstrate that olaparib with
bevacizumab reduces the risk of death by 38% in HRD-positive
patients compared to bevacizumab alone, further reinforcing the
clinically meaningful long-term survival benefit of this
combination. This should be promising news for both clinicians and
patients, as we see these additional data show that this
combination may allow patients more time with family and loved
ones. These results also highlight the importance of biomarker
testing as part of a precision medicine approach to guide treatment
decisions in ovarian cancer patients.”
Professor Paul DiSilvestro, investigator from the SOLO-1 trial
and Director of the Program in Women’s Oncology at Women and
Infants Hospital in Providence, Rhode Island, said: “The long-term
results from SOLO-1 confirm that olaparib continues to elicit a
clinically meaningful improvement in overall survival in the
1st-line maintenance setting for more than seven years. Achieving
long-term survival for patients with newly diagnosed advanced
ovarian cancer is critical because the first line setting offers
the greatest potential to impact patient survival.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “Historically the five-year survival rate of
newly diagnosed patients with advanced ovarian cancer is 30-50%. In
that context, it is phenomenal to share the long-term overall
survival data from both PAOLA-1 and SOLO-1, with two out of three
patients still alive in these trials. We continue to believe in
LYNPARZA’s ability to help biomarker-selected patients with
advanced ovarian cancer to achieve better outcomes.”
Dr. Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, Merck Research Laboratories,
said: “These latest data from the PAOLA-1 and SOLO-1 trials further
highlight the importance of HRD testing, including for BRCA1/2
mutations, for all newly diagnosed advanced ovarian cancer patients
at the point of diagnosis. Maintenance therapy with LYNPARZA may
provide certain patients with HRD-positive and/or BRCA-mutated
advanced ovarian cancer the opportunity to live longer.”
Updated results from the PAOLA-1 Phase
III trial
Updated results from the PAOLA-1 Phase III trial demonstrate
that LYNPARZA plus bevacizumab increased median overall survival to
56.5 months versus 51.6 months with bevacizumab alone, in patients
with newly diagnosed advanced ovarian cancer irrespective of HRD
status. This increase was not statistically significant.
In HRD-positive patients, LYNPARZA plus bevacizumab provided a
clinically meaningful improvement in overall survival, reducing the
risk of death by 38% versus bevacizumab (based on a HR of 0.62; 95%
CI 0.45-0.85) despite PAOLA-1 having 30% Stage IV patients. 65.5%
of patients treated with LYNPARZA plus bevacizumab were still alive
at five years versus 48.4% of those treated with bevacizumab alone.
LYNPARZA plus bevacizumab also improved median PFS to almost four
years (46.8 months) versus 17.6 months with bevacizumab plus
placebo and 46.1% of patients treated with LYNPARZA plus
bevacizumab remain progression free at five years versus 19.2% of
patients treated with bevacizumab alone. The safety and
tolerability profile of LYNPARZA in this trial was in line with
that observed in prior clinical trials, with no new safety
signals.
Updated results from the SOLO-1 Phase
III trial
Updated results from the SOLO-1 Phase III trial demonstrate that
LYNPARZA provided a clinically meaningful improvement in overall
survival (OS) versus placebo in patients with BRCA-mutated (BRCAm)
newly diagnosed advanced ovarian cancer, reducing the risk of death
by 45% (based on an HR of 0.55; 95% CI 0.40-0.76; nominal p=0.0004
[not statistically significant]). Median OS was still not reached
with LYNPARZA versus 75.2 months with placebo. At the seven-year
descriptive OS analysis, 67% of LYNPARZA patients were alive versus
47% of placebo patients (44% of whom had a subsequent PARP
inhibitor) and 45% of LYNPARZA patients versus 21% of placebo
patients were alive and had not received a first subsequent
treatment.
Additional data showed median time to first subsequent therapy
was 64 months with LYNPARZA versus 15.1 months with placebo. The
safety and tolerability profile of LYNPARZA in this trial was in
line with that observed in prior clinical trials, with no new
safety signals.
Summary of results
PAOLA-1
LYNPARZA + bevacizumab
(n=537)
Placebo + bevacizumab
(n=269)
OS1
Number of patients with events (%)
288 (53.6)
158 (58.7)
Median OS (in months)
56.5
51.6
HR (95% CI)
p-value
0.92 (0.76,1.12)
0.4118
OS by HRD status2
HRD positive (including tBRCAm)
Number of patients randomized
255
132
Number of patients with events (%)
93 (36.5)
69 (52.3)
Median (in months)
75.2
57.3
HR (95% CI)
0.62 (0.45, 0.85)
HRD positive (excluding tBRCAm)
Number of patients randomized
97
55
Number of patients with events (%)
44 (45.4)
32 (58.2)
Median (in months)
Not reached
52.0
HR (95% CI)
0.71 (0.45, 1.13)
BRCAm
Number of patients randomized
157
80
Number of patients with events (%)
48 (30.6)
37 (46.3)
Median (in months)
75.2
66.9
HR (95% CI)
0.60 (0.39, 0.93)
HRD negative
Number of patients randomized
192
85
Number of patients with events (%)
140 (72.9)
58 (68.2)
Median (95% CI) (in months)
36.8
40.4
HR (95% CI)
1.19 (0.88, 1.63)
PFS3 by HRD status2
HRD positive (including tBRCAm)
Number of patients randomized
255
132
Number of patients with events (%)
136 (53.3)
104 (78.8)
Median (in months)
46.8
17.6
HR (95% CI)
0.41 (0.32, 0.54)
SOLO-1
LYNPARZA
(n=260)
Placebo
(n=131)
OS4
Number of patients with events (%)
84 (32.2)
65 (49.6)
Median OS (in months)
Not reached
75.2
HR (95% CI)
p-value5
0.55 (0.40, 0.76)
0.0004
Time to first subsequent
therapy
Number of patients with events (%)
135 (51.9)
98 (74.8)
Median (95% CI) (in months)
64.0
15.1
HR (95% CI)
0.37 (0.28–0.48)
Time to second subsequent
therapy
Number of patients with events (%)
110 (42.3)
80 (61.1)
Median (95% CI) (in months)
93.2
40.7
HR (95% CI)
0.5 (0.37, 0.67)
1. OS analysis was done at 56% maturity
(448 events in 797 patients) and boundary for significance 0.0001;
statistical significance not reached.
2. Exploratory subgroup analysis by HRD
status. The HRD status of patients in PAOLA-1 was determined from
post-randomization testing of tumor samples using the Myriad
myChoice HRD plus test
3. Investigator-assessed PFS (RECIST
1.1)
4. OS analysis was done at 38.1% maturity
(149 events in 391 patients) and boundary for significance 0.01;
statistical significance not reached. Survival follow up continues
and further analyses were planned.
5. P<0.0001 required to declare
statistical significance
LYNPARZA is approved as 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 HRD-positive advanced ovarian
cancer, respectively.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia
(MDS/AML): Occurred in approximately 1.5% of patients exposed
to LYNPARZA monotherapy, and the majority of events had a fatal
outcome. The median duration of therapy in patients who developed
MDS/AML was 2 years (range: <6 months to >10 years). All of
these patients had previous chemotherapy with platinum agents
and/or other DNA-damaging agents, including radiotherapy.
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.
Embryo-Fetal Toxicity: Based on its mechanism of action
and findings in animals, LYNPARZA can cause fetal harm. A pregnancy
test is recommended for 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.
Venous Thromboembolic Events: Including pulmonary
embolism, occurred in 7% of patients with metastatic
castration-resistant prostate cancer who received LYNPARZA plus
androgen deprivation therapy (ADT) compared to 3.1% of patients
receiving enzalutamide or abiraterone plus ADT in the PROfound
study. Patients receiving LYNPARZA and ADT had a 6% incidence of
pulmonary embolism compared to 0.8% of patients treated with ADT
plus either enzalutamide or abiraterone. 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.
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 compared to a ≥5% frequency for
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 thromboembolic events 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 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%).
Study 19: nausea (71%), fatigue (including asthenia)
(63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory
tract infection (22%), constipation (22%), headache (21%),
decreased appetite (21%), and dyspepsia (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the maintenance setting
(SOLO-2/Study 19) were: increase in mean corpuscular volume
(89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes
(69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute
neutrophil count (51%/47%), increase in serum creatinine (44%/45%),
and decrease in platelets (42%/36%).
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%).
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 Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer,
who are in complete or partial response to platinum-based
chemotherapy.
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.
Please see complete Prescribing
Information, including Medication Guide.
Notes
Ovarian cancer
Ovarian cancer is the eighth most common cancer in women
worldwide.9 There were more than 313,000 new cases of ovarian
cancer in 2020, and over 207,000 deaths. The 5-year survival rate
of newly diagnosed advanced ovarian cancer patients has typically
been 30-50%.4,5 Roughly half of women with advanced ovarian cancer
have homologous recombination deficiency (HRD)-positive tumors
including those with a BRCA mutation and up to one in five women
have a BRCA mutation.6-8 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.10-12
PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy
and safety of LYNPARZA added to standard-of-care bevacizumab versus
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 Merck
announced in August 2019 that the trial met its primary endpoint of
PFS in the overall trial population.
PAOLA-1 is an ENGOT (European Network of Gynaecological
Oncological Trial groups) trial, sponsored by ARCAGY Research
(Association de Recherche sur les CAncers dont GYnécologiques) on
behalf of GINECO (Groupe d’Investigateurs National des Etudes des
Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group
specializing in clinical and translational research in patients’
cancers and a member of the GCIG (Gynecologic Cancer
InterGroup).
SOLO-1
SOLO-1 is a Phase III randomized, double-blinded,
placebo-controlled, multicenter trial to evaluate the efficacy and
safety of LYNPARZA tablets (300 mg twice daily) as maintenance
monotherapy compared with placebo, in newly-diagnosed patients with
advanced BRCAm ovarian cancer following platinum-based
chemotherapy. The trial randomized 391 patients with a deleterious
or suspected deleterious BRCA1 or BRCA2 mutation who were in
clinical complete or partial response following platinum-based
chemotherapy. Patients were randomized (2:1) to receive LYNPARZA or
placebo for up to two years or until disease progression (at the
investigator’s discretion). The primary endpoint was PFS and key
secondary endpoints included time to second disease progression or
death, time to first subsequent treatment and overall survival.
AstraZeneca and MSD announced in June 2018 that the trial met its
primary endpoint of PFS in the overall trial population.
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.13 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 alterations that can lead to
cancer. Cancers with BRCA mutations are more likely to be sensitive
to PARP inhibitors including LYNPARZA.13-16
Homologous recombination deficiency
HRD, which defines a subgroup 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.2
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
repair (HRR), 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 proteins 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 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, HER2-negative metastatic breast cancer
(in the EU and Japan this includes locally advanced breast cancer);
for gBRCAm, HER2-negative high-risk early breast cancer (in Japan
this includes all BRCAm HER2-negative high-risk early breast
cancer); for gBRCAm metastatic pancreatic cancer; and HRR
gene-mutated metastatic castration-resistant prostate cancer (BRCAm
only in the EU and Japan).
LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck, is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and Merck 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.
About 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 100 countries and its innovative
medicines are used by millions of patients worldwide. Please visit
www.astrazeneca-us.com and follow the Company on Twitter
@AstraZenecaUS.
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US- 68342 Last Updated 09/22
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version on businesswire.com: https://www.businesswire.com/news/home/20220909005080/en/
Media Inquiries Brendan McEvoy +1 302 885 2677 Jessica
McDuell +1 302 885 2677 US Media Mailbox:
usmediateam@astrazeneca.com
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