Five-year follow-up of the Phase 3 PAOLA-1
trial showed LYNPARZA plus bevacizumab provided a clinically
meaningful improvement in overall survival in a subgroup of
HRD-positive patients, with 65.5% of patients still alive versus
48.4% who received bevacizumab and placebo
The Phase 3 SOLO-1 trial demonstrated 67% of
advanced ovarian cancer patients with BRCA mutations receiving
LYNPARZA were alive at seven years versus 47% of placebo patients,
the longest follow-up for any PARP inhibitor in this
setting
AstraZeneca and Merck, known as MSD outside of the United States
and Canada, today announced long-term follow-up results from the
Phase 3 PAOLA-1 and SOLO-1 trials in first-line advanced ovarian
cancer, which represent the longest-term data for any PARP
inhibitor in this setting.
These results were presented on Sept. 9 at the European Society
for Medical Oncology (ESMO) 2022 Congress, and the SOLO-1 results
were published in the Journal of Clinical Oncology.
Ovarian cancer is one of the most common gynecologic cancers and
has the worst prognosis and highest mortality rate. More than
two-thirds of patients with ovarian cancer are diagnosed with
advanced disease, and approximately 50-70% of these patients die
within five years. Roughly half of patients with advanced ovarian
cancer have homologous recombination deficiency (HRD)-positive
tumors, including those with a BRCA mutation, and one in four women
have a BRCA mutation.
Five-year follow-up and final OS results from Phase 3 PAOLA-1
trial (abstract #LBA29)
The Phase 3 PAOLA-1 trial evaluated LYNPARZA in combination with
bevacizumab as first-line maintenance therapy in patients with
advanced ovarian cancer, who were without evidence of disease after
surgery or following response to platinum-based chemotherapy. Final
overall survival (OS), a key secondary endpoint, in those who
received LYNPARZA plus bevacizumab was 56.5 months versus 51.6
months with bevacizumab alone (HR=0.92 [95% CI, 0.76-1.12];
p=0.4118) in patients with newly diagnosed advanced ovarian cancer.
These OS results were not statistically significant.
In an exploratory subgroup analysis of HRD-positive patients,
LYNPARZA plus bevacizumab provided a clinically meaningful
improvement in OS, reducing the risk of death by 38% (HR=0.62 [95%
CI, 0.45-0.85]) versus bevacizumab alone. 65.5% of patients who
received LYNPARZA plus bevacizumab were still alive at five years
versus 48.4% who received bevacizumab alone. LYNPARZA plus
bevacizumab also improved median progression-free survival (PFS) to
nearly four years (46.8 months) versus 17.6 months with bevacizumab
plus placebo, and 46.1% of patients who received LYNPARZA in
combination with bevacizumab remain progression free versus 19.2%
of patients who received 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.
Adverse events of special interest for LYNPARZA in combination with
bevacizumab versus bevacizumab alone included myelodysplastic
syndrome/acute myeloid leukemia/aplastic anemia (1.7% vs. 2.2%),
new primary malignancies (4.1% vs. 3.0%) and
pneumonitis/interstitial lung disease/bronchiolitis (1.3% vs.
0.7%).
Seven-year follow-up from Phase 3 SOLO-1 trial (abstract
#517O)
The Phase 3 SOLO-1 trial evaluated LYNPARZA as monotherapy as
first-line maintenance therapy in patients with advanced ovarian
cancer, who were without evidence of disease after surgery or
following response to platinum-based chemotherapy. In the trial,
LYNPARZA demonstrated a clinically meaningful improvement in OS
versus placebo in patients with germline BRCA-mutated (gBRCAm)
newly diagnosed advanced ovarian cancer, reducing the risk of death
by 45% (HR=0.55 [95% CI, 0.40-0.76]; p=0.0004) versus placebo (not
statistically significant). Median OS was 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
(TFST) was 64.0 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. The most common treatment-emergent adverse
events (≥20%) were nausea (78%), fatigue (64%), vomiting (40%),
anemia (40%), diarrhea (35%), arthralgia (29%), constipation (28%),
abdominal pain (26%), headache (23%), neutropenia (23%), dysgeusia
(22%), dizziness (20%) and decreased appetite (20%).
Please see Important Safety Information for LYNPARZA after the
“About SOLO-1” section below.
Professor Isabelle Ray-Coquard, principal investigator from the
PAOLA-1 trial and president of the GINECO group said, “For women
facing an advanced ovarian cancer diagnosis who are HRD-positive, a
targeted treatment in the first-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 Di Silvestro, 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 LYNPARZA continues to elicit a
clinically meaningful improvement in overall survival in the
first-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 or BRCA-mutated advanced
ovarian cancer the opportunity to live longer.”
Summary of PAOLA-1 & SOLO-1 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 OS (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 OS (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 OS (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 OS (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 OS (in months)
46.8
17.6
HR (95% CI)
0.41 (0.32, 0.54)
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 was determined from
post-randomization testing of tumor samples using the Myriad
myChoice HRD plus test. 3. Investigator-assessed PFS (RECIST 1.1)
SOLO-1
LYNPARZA (n=260)
Placebo (n=131)
OS1
Number of patients with events (%)
84 (32.2)
65 (49.6)
Median OS (in months)
Not reached
75.2
HR (95% CI) p-value2
0.55 (0.40, 0.76) 0.0004
TFST
Number of patients with events (%)
135 (51.9)
98 (74.8)
Median OS (in months)
64.0
15.1
HR (95% CI)
0.37 (0.28, 0.48)
Time to second subsequent therapy
(TSST)
Number of patients with events (%)
110 (42.3)
80 (61.1)
Median TSST (in months)
93.2
40.7
HR (95% CI)
0.5 (0.37, 0.67)
1. 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.
2. 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 first-line maintenance
treatment of BRCAm and HRD-positive advanced ovarian cancer,
respectively. Select patients for therapy based on an FDA-approved
companion diagnostic for LYNPARZA.
About PAOLA-1
PAOLA-1 is a Phase 3, double-blinded trial evaluating the
efficacy and safety of LYNPARZA added to standard-of-care
bevacizumab versus bevacizumab alone as a first-line maintenance
treatment for patients with newly diagnosed advanced FIGO stage
III-IV high-grade serous or endometroid ovarian, fallopian tube or
peritoneal cancer who had a complete or partial response to
first-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).
About SOLO-1
SOLO-1 is a Phase 3, randomized, double-blinded,
placebo-controlled, multicenter trial to evaluate the efficacy and
safety of LYNPARZA (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,
TFST and OS. AstraZeneca and Merck announced in June 2018 that the
trial met its primary endpoint of PFS in the overall trial
population.
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 for LYNPARZA in the United States
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated for:
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.
About LYNPARZA® (olaparib)
LYNPARZA is a first-in-class PARP inhibitor and the first
targeted treatment to potentially exploit DNA damage response (DDR)
pathway deficiencies, such as BRCA mutations, to preferentially
kill cancer cells. Inhibition of PARP with LYNPARZA leads to the
trapping of PARP bound to DNA single-strand breaks, stalling of
replication forks, their collapse and the generation of DNA
double-strand breaks and cancer cell death. LYNPARZA is being
tested in a range of tumor types with defects and dependencies in
the DDR.
LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck, has a broad and advanced clinical trial
development program, and AstraZeneca and Merck are working together
to understand how it may affect multiple PARP-dependent tumors as a
monotherapy and in combination across multiple cancer types.
About ovarian cancer
Ovarian cancer is the eighth most common cancer in women
worldwide. Globally, there were more than 313,000 new cases of
ovarian cancer in 2020 and over 207,000 deaths. The five-year
survival rate newly diagnosed advanced ovarian cancer patients has
typically been 30-50%. Roughly half of women with advanced ovarian
cancer have homologous recombination deficiency (HRD)-positive
tumors, including those with a BRCA mutation, and one in four women
have a BRCA mutation. The primary aim of first-line treatment is to
delay disease progression for as long as possible with the intent
to achieve long-term remission.
About BRCA mutations
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are
human genes that produce proteins responsible for repairing damaged
DNA and play an important role maintaining the genetic stability of
cells. When either of these genes is mutated or altered such that
its protein product either is not made or does not function
correctly, DNA damage may not be repaired properly, and cells
become unstable. As a result, cells are more likely to develop
additional genetic alterations that can lead to cancer.
About homologous recombination deficiency
Homologous recombination deficiency, 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.
About the AstraZeneca and Merck strategic oncology
collaboration
In July 2017, AstraZeneca and Merck, known as MSD outside of the
United States and Canada, announced a global strategic oncology
collaboration to co-develop and co-commercialize certain oncology
products including LYNPARZA, the world’s first PARP inhibitor, for
multiple cancer types. Working together, the companies will develop
these products in combination with other potential new medicines
and as monotherapies. Independently, the companies will develop
these oncology products in combination with their respective PD-L1
and PD-1 medicines.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck,
the potential to bring new hope to people with cancer drives our
purpose and supporting accessibility to our cancer medicines is our
commitment. As part of our focus on cancer, Merck is committed to
exploring the potential of immuno-oncology with one of the largest
development programs in the industry across more than 30 tumor
types. We also continue to strengthen our portfolio through
strategic acquisitions and are prioritizing the development of
several promising oncology candidates with the potential to improve
the treatment of advanced cancers. For more information about our
oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada,
we are unified around our purpose: We use the power of leading-edge
science to save and improve lives around the world. For more than
130 years, we have brought hope to humanity through the development
of important medicines and vaccines. We aspire to be the premier
research-intensive biopharmaceutical company in the world – and
today, we are at the forefront of research to deliver innovative
health solutions that advance the prevention and treatment of
diseases in people and animals. We foster a diverse and inclusive
global workforce and operate responsibly every day to enable a
safe, sustainable and healthy future for all people and
communities. For more information, visit www.merck.com and connect
with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Rahway,
N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA
(the “company”) includes “forward-looking statements” within the
meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline candidates that
the candidates will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of the global outbreak of novel coronavirus disease
(COVID-19); the impact of pharmaceutical industry regulation and
health care legislation in the United States and internationally;
global trends toward health care cost containment; technological
advances, new products and patents attained by competitors;
challenges inherent in new product development, including obtaining
regulatory approval; the company’s ability to accurately predict
future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign
risk; dependence on the effectiveness of the company’s patents and
other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s Annual
Report on Form 10-K for the year ended December 31, 2021 and the
company’s other filings with the Securities and Exchange Commission
(SEC) available at the SEC’s Internet site (www.sec.gov).
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version on businesswire.com: https://www.businesswire.com/news/home/20220909005050/en/
Media: Melissa Moody, (215) 407-3536 Chrissy Trank, (640)
650-0694
Investor: Peter Dannenbaum, (908) 740-1037 Damini Chokshi, (908)
740-1807
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