Positive results from a planned interim analysis of the DUO-O
Phase III trial showed that treatment with a combination of
LYNPARZA® (olaparib), IMFINZI® (durvalumab), chemotherapy and
bevacizumab demonstrated a statistically significant and clinically
meaningful improvement in progression-free survival (PFS) versus
chemotherapy plus bevacizumab (control arm) in newly diagnosed
patients with advanced high-grade epithelial ovarian cancer without
tumor BRCA mutations. Patients were treated with IMFINZI in
combination with chemotherapy and bevacizumab followed by IMFINZI,
LYNPARZA and bevacizumab as maintenance therapy.
These results will be presented today in an oral presentation at
the 2023 American Society of Clinical Oncology (ASCO) Annual
Meeting in Chicago (Abstract #LBA5506).
The combination of LYNPARZA, IMFINZI, chemotherapy and
bevacizumab reduced the relative risk of disease progression or
death by 37% versus chemotherapy and bevacizumab (hazard ratio (HR)
0.63; 95% CI 0.52-0.76; p<0.0001). Median PFS was 24.2 months
versus 19.3, respectively. In the homologous recombination
deficiency (HRD)-positive subgroup of patients, LYNPARZA, IMFINZI,
chemotherapy and bevacizumab reduced the relative risk of disease
progression or death by 51% versus chemotherapy and bevacizumab
alone (HR 0.49; 95% CI 0.34-0.69; p<0.0001). Median PFS was 37.3
months versus 23.0, respectively.
Professor Philipp Harter, Director, Department of Gynaecology
and Gynaecologic Oncology, Evangelische Kliniken Essen-Mitte,
Germany, and principal investigator for the trial, said: “The
primary aim of first-line treatment of patients with advanced
ovarian cancer is long-term control over the disease, but still too
many patients progress quickly and face poor clinical outcomes
today. Data from the DUO-O trial interim progression-free survival
analysis provide evidence for further improvement with olaparib and
durvalumab combination versus chemotherapy and bevacizumab alone in
patients without tumor BRCA mutations.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “These results are an important milestone in our
ongoing journey to address unmet need in ovarian cancer. The DUO-O
trial demonstrates the potential of combining PARP inhibition with
immunotherapy and we look forward to seeing more mature data and
key secondary endpoints results.”
At a pre-planned exploratory analysis of the HRD-negative
subgroup of patients, LYNPARZA, IMFINZI, chemotherapy and
bevacizumab reduced the relative risk of disease progression or
death by 32% versus chemotherapy and bevacizumab (HR 0.68; 95% CI
0.54-0.86). Median PFS was 20.9 months versus 17.4.
At the time of this interim analysis, an additional arm
evaluating the combination of IMFINZI, chemotherapy and bevacizumab
demonstrated a numerical improvement in PFS which was not
statistically significant (HR 0.87; 95% CI 0.73-1.04; p=0.13).
At the time of this planned interim analysis, the overall
survival (OS) and other secondary endpoints were immature. OS will
be formally assessed at a subsequent analysis.
Summary of results: DUO-O
Arm 1 chemotherapy and
bevacizumab (n=378)
Arm 2 IMFINZI, chemotherapy and
bevacizumab (n=374)
Arm 3 LYNPARZA, IMFINZI,
chemotherapy and bevacizumab (n=378)
ITT
Events, n/N (%)
259 (69)
226 (60)
193 (51)
Median PFS, months
19.3
20.6
24.2
HR (95% CI) vs. arm 1
0.87 (0.73-1.04)
p=0.13*
0.63 (0.52-0.76)
p<0.0001*
HRD-positive
Events, n/N (%)
86 (60)
69 (47)
49 (35)
Median PFS, months
23.0
24.4
37.3
HR (95% CI) vs. arm 1
0.82 (0.60-1.12)
0.49** (0.34-0.69)
p<0.0001*
HRD-negative (based on an
exploratory analysis)
Events, n/N (%)
157 (73)
142 (71)
127 (60)
Median PFS, months
17.4
15.4
20.9
HR (95% CI) vs. arm 1
0.94 (0.75-1.18)
0.68 (0.54-0.86)
*Results based on the stratified model
**Results based on the unstratified model: HR 0.51 (95% CI
0.36-0.72)
The safety and tolerability of these combinations was broadly
consistent with that observed in prior clinical trials and the
known profiles of the individual medicines.
The most common adverse events (AEs) (greater than or equal to
20% of patients) for the combination of LYNPARZA, IMFINZI,
chemotherapy and bevacizumab were nausea (57%), anemia (55%),
neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%),
constipation (30%), diarrhea (30%), thrombocytopenia (28%),
hypertension (26%), vomiting (26%), leukopenia (24%), headache
(22%), abdominal pain (21%) and hypothyroidism (20%). Grade 3 or
higher AEs were neutropenia (31%), anemia (24%), leukopenia (8%),
hypertension (7%) and thrombocytopenia (6%).
Approximately 65% of patients treated with the combination of
LYNPARZA, IMFINZI, chemotherapy and bevacizumab who experienced AEs
during chemotherapy and throughout the maintenance phase remained
on treatment at the time of data cut-off, compared to 80% of
patients in the control arm (chemotherapy plus bevacizumab).
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.
Venous Thromboembolism (VTE): Including severe or fatal
pulmonary embolism (PE) occurred in patients treated with LYNPARZA.
In the combined data of two randomized, placebo-controlled clinical
studies (PROfound and PROpel) in patients with metastatic
castration-resistant prostate cancer (N=1180), VTE occurred in 8%
of patients who received LYNPARZA, including pulmonary embolism in
6%. In the control arms, VTE occurred in 2.5%, including pulmonary
embolism in 1.5%. Monitor patients for signs and symptoms of venous
thrombosis and pulmonary embolism, and treat as medically
appropriate, which may include long-term anticoagulation as
clinically indicated.
Embryo-Fetal Toxicity: Based on its mechanism of action
and findings in animals, LYNPARZA can cause fetal harm. Verify
pregnancy status in females of reproductive potential prior to
initiating treatment.
Females
Advise females of reproductive potential of the potential risk
to a fetus and to use effective contraception during treatment and
for 6 months following the last dose.
Males
Advise male patients with female partners of reproductive
potential or who are pregnant to use effective contraception during
treatment and for 3 months following the last dose of LYNPARZA and
to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced
Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA in the first-line maintenance setting
for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain
(45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation
(28%), upper respiratory tract
infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia
(26%), decreased appetite (20%), dizziness (20%), neutropenia
(17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary
tract infection (13%), thrombocytopenia (11%), and stomatitis
(11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the first-line maintenance
setting for SOLO-1 were: decrease in hemoglobin (87%),
increase in mean corpuscular volume (87%), decrease in leukocytes
(70%), decrease in lymphocytes (67%), decrease in absolute
neutrophil count (51%), decrease in platelets (35%), and increase
in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian
Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients
treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared
to placebo/bevacizumab in the first-line maintenance setting
for PAOLA-1 were: nausea (53%), fatigue (including asthenia)
(53%), anemia (41%), lymphopenia (24%), vomiting (22%), and
leukopenia (18%). In addition, the most common adverse reactions
(≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of
the frequency compared with the placebo/bevacizumab arm were:
diarrhea (18%), neutropenia (18%), urinary tract infection (15%),
and headache (14%).
In addition, venous 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%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate
Cancer in Combination with Abiraterone and Prednisone or
Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA/abiraterone with a difference of ≥5% compared
to placebo for PROpel were: anemia (48%), fatigue (including
asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite
(16%), lymphopenia (14%), dizziness (14%), and abdominal pain
(13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of
patients who received LYNPARZA/abiraterone for PROpel were:
decrease in hemoglobin (97%), decrease in lymphocytes (70%),
decrease in platelets (23%), and decrease in absolute neutrophil
count (23%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with
other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of
myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or
moderate CYP3A inhibitors when using LYNPARZA. If a strong or
moderate CYP3A inhibitor must be coadministered, reduce the dose of
LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice,
Seville oranges, and Seville orange juice during LYNPARZA
treatment.
CYP3A Inducers: Avoid coadministration of strong or
moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence
of olaparib in human milk, its effects on the breastfed infant or
on milk production. Because of the potential for serious adverse
reactions in the breastfed infant, advise a lactating woman not to
breastfeed during treatment with LYNPARZA and for 1 month after
receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have
not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild or moderate hepatic impairment
(Child-Pugh classification A and B). There are no data in patients
with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended
in patients with mild renal impairment (CLcr 51-80 mL/min estimated
by Cockcroft-Gault). In patients with moderate renal impairment
(CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice
daily. There are no data in patients with severe renal impairment
or end-stage renal disease (CLcr ≤30 mL/min).
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious
or suspected deleterious germline or somatic BRCA-mutated (gBRCAm
or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in complete or partial response to
first-line platinum-based chemotherapy. Select patients for therapy
based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer
in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of
adult patients with advanced epithelial ovarian, fallopian tube or
primary peritoneal cancer who are in complete or partial response
to first-line platinum-based chemotherapy and whose cancer is
associated with homologous recombination deficiency (HRD)-positive
status defined by either:
- a deleterious or suspected deleterious BRCA mutation,
and/or
- genomic instability
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.
Maintenance 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.
BRCAm Metastatic Castration-Resistant Prostate Cancer in
Combination with Abiraterone and Prednisone or Prednisolone
In combination with abiraterone and prednisone or prednisolone
(abi/pred) for the treatment of adult patients with deleterious or
suspected deleterious BRCA-mutated (BRCAm) metastatic
castration-resistant prostate cancer (mCRPC). Select patients for
therapy based on an FDA-approved companion diagnostic for
LYNPARZA.
Please see complete Prescribing Information, including
Medication Guide.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab) or
IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under
Warnings and Precautions may not include all possible severe and
fatal immune-mediated reactions. Immune-mediated adverse reactions,
which may be severe or fatal, can occur in any organ system or
tissue. Immune-mediated adverse reactions can occur at any time
after starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate clinical
chemistries including liver enzymes, creatinine,
adrenocorticotropic hormone (ACTH) level, and thyroid function at
baseline and before each dose. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO
depending on severity. See USPI Dosing and Administration for
specific details. In general, if IMFINZI and IMJUDO requires
interruption or discontinuation, administer systemic corticosteroid
therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until
improvement to Grade 1 or less. Upon improvement to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at
least 1 month. Consider administration of other systemic
immunosuppressants in patients whose immune-mediated adverse
reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which
may be fatal. The incidence of pneumonitis is higher in patients
who have received prior thoracic radiation.
- IMFINZI as a Single Agent
- In patients who did not receive recent prior radiation, the
incidence of immune-mediated pneumonitis was 2.4% (34/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of
pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3%
(87/475) in patients receiving IMFINZI and 12.8% (30/234) in
patients receiving placebo. Of the patients who received IMFINZI
(475), 1.1% were fatal and 2.7% were Grade 3 adverse
reactions.
- The frequency and severity of immune-mediated pneumonitis in
patients who did not receive definitive chemoradiation prior to
IMFINZI were similar in patients who received IMFINZI as a single
agent or with ES-SCLC or BTC when in combination with
chemotherapy.
- IMFINZI with IMJUDO
- Immune-mediated pneumonitis occurred in 1.3% (5/388) of
patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and
Grade 3 (0.2%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated pneumonitis occurred in 3.5% (21/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including fatal (0.5%), and Grade 3
(1%) adverse reactions.
Immune-Mediated Colitis
IMFINZI and IMJUDO can cause immune-mediated colitis that is
frequently associated with diarrhea. Cytomegalovirus (CMV)
infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies.
- IMFINZI as a Single Agent
- Immune-mediated colitis occurred in 2% (37/1889) of patients
receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%)
adverse reactions.
- IMFINZI with IMJUDO
- Immune-mediated colitis or diarrhea occurred in 6% (23/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%)
adverse reactions. Intestinal perforation has been observed in
other studies of IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated colitis occurred in 6.5% (39/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse
reactions. Intestinal perforation and large intestine perforation
were reported in 0.1% of patients.
- Immune-Mediated Hepatitis
- IMFINZI and IMJUDO can cause immune-mediated hepatitis, which
may be fatal.
- IMFINZI as a Single Agent
- Immune-mediated hepatitis occurred in 2.8% (52/1889) of
patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%)
and Grade 3 (1.4%) adverse reactions.
- IMFINZI with IMJUDO
- Immune-mediated hepatitis occurred in 7.5% (29/388) of patients
receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4
(0.3%) and Grade 3 (4.1%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hepatitis occurred in 3.9% (23/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3
(2%) adverse reactions.
Immune-Mediated Endocrinopathies
Adrenal Insufficiency: IMFINZI and IMJUDO can cause
primary or secondary adrenal insufficiency. For Grade 2 or higher
adrenal insufficiency, initiate symptomatic treatment, including
hormone replacement as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889)
of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated adrenal insufficiency occurred in 1.5% (6/388)
of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated adrenal insufficiency occurred in 2.2% (13/596)
of patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.8%) adverse
reactions.
Hypophysitis: IMFINZI and IMJUDO can cause
immune-mediated hypophysitis. Hypophysitis can present with acute
symptoms associated with mass effect such as headache, photophobia,
or visual field cuts. Hypophysitis can cause hypopituitarism.
Initiate symptomatic treatment including hormone replacement as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 hypophysitis/hypopituitarism occurred in <0.1%
(1/1889) of patients who received IMFINZI.
- IMFINZI with IMJUDO
- Immune-mediated hypophysitis/hypopituitarism occurred in 1%
(4/388) of patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hypophysitis occurred in 1.3% (8/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
Thyroid Disorders (Thyroiditis, Hyperthyroidism, and
Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy.
Hypothyroidism can follow hyperthyroidism. Initiate hormone
replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated thyroiditis occurred in 0.5% (9/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of
patients receiving IMFINZI.
- Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated thyroiditis occurred in 1.5% (6/388) of
patients receiving IMFINZI and IMJUDO.
- Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- Immune-mediated hypothyroidism occurred in 11% (42/388) of
patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated thyroiditis occurred in 1.2% (7/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy.
- Immune-mediated hyperthyroidism occurred in 5% (30/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.2%) adverse
reactions.
- Immune-mediated hypothyroidism occurred in 8.6% (51/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 immune-mediated Type 1 diabetes mellitus occurred in
<0.1% (1/1889) of patients receiving IMFINZI.
- IMFINZI with IMJUDO
- Two patients (0.5%, 2/388) had events of hyperglycemia
requiring insulin therapy that had not resolved at last
follow-up.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated Type 1 diabetes mellitus occurred in 0.5%
(3/596) of patients receiving IMFINZI in combination with IMJUDO
and platinum-based chemotherapy including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI and IMJUDO can cause immune-mediated
nephritis.
- IMFINZI as a Single Agent
- Immune-mediated nephritis occurred in 0.5% (10/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated nephritis occurred in 1% (4/388) of patients
receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated nephritis occurred in 0.7% (4/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology
Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis.
Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS),
drug rash with eosinophilia and systemic symptoms (DRESS), and
toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1 and
CTLA-4 blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-exfoliative rashes.
- IMFINZI as a Single Agent
- Immune-mediated rash or dermatitis occurred in 1.8% (34/1889)
of patients receiving IMFINZI, including Grade 3 (0.4%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of
patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and
Grade 3 (1.5%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of
patients receiving IMFINZI in combination with IMJUDO in
combination with platinum-based chemotherapy, including Grade 3
(0.3%) adverse reactions.
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated
pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388)
of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%)
and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse
Reactions
The following clinically significant, immune-mediated adverse
reactions occurred at an incidence of less than 1% each in patients
who received IMFINZI and IMJUDO or were reported with the use of
other immune-checkpoint inhibitors.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism.
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening
infusion-related reactions. Monitor for signs and symptoms of
infusion-related reactions. Interrupt, slow the rate of, or
permanently discontinue IMFINZI and IMJUDO based on the severity.
See USPI Dosing and Administration for specific details. For Grade
1 or 2 infusion-related reactions, consider using pre-medications
with subsequent doses.
- IMFINZI as a Single Agent
- Infusion-related reactions occurred in 2.2% (42/1889) of
patients receiving IMFINZI, including Grade 3 (0.3%) adverse
reactions.
- IMFINZI with IMJUDO
- Infusion-related reactions occurred in 10 (2.6%) patients
receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Infusion-related reactions occurred in 2.9% (17/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies,
IMFINZI and IMJUDO can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. In females of reproductive potential, verify pregnancy
status prior to initiating IMFINZI and IMJUDO and advise them to
use effective contraception during treatment with IMFINZI and
IMJUDO and for 3 months after the last dose of IMFINZI and
IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and
IMJUDO in human milk; however, because of the potential for serious
adverse reactions in breastfed infants from IMFINZI and IMJUDO,
advise women not to breastfeed during treatment and for 3 months
after the last dose.
Adverse Reactions
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), the most common adverse reactions (≥20%) were
cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis
(34%), upper respiratory tract infections (26%), dyspnea (25%), and
rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%)
were pneumonia (7%) and pneumonitis/radiation pneumonitis
(3.4%).
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), discontinuation due to adverse reactions occurred
in 15% of patients in the IMFINZI arm. Serious adverse reactions
occurred in 29% of patients receiving IMFINZI. The most frequent
serious adverse reactions (≥2%) were pneumonitis or radiation
pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation
pneumonitis and fatal pneumonia occurred in <2% of patients and
were similar across arms.
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
and IMJUDO plus platinum-based chemotherapy (n=330), the most
common adverse reactions (occurring in ≥20% of patients) were
nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased
appetite (28%), rash (27%), and diarrhea (22%).
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
in combination with IMJUDO and platinum-based chemotherapy (n=330),
permanent discontinuation of IMFINZI or IMJUDO due to an adverse
reaction occurred in 17% of patients. Serious adverse reactions
occurred in 44% of patients, with the most frequent serious adverse
reactions reported in at least 2% of patients being pneumonia
(11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%),
pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse
reactions occurred in a total of 4.2% of patients.
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), the most common
adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%),
and alopecia (31%). The most common Grade 3 or 4 adverse reaction
(≥3%) was fatigue/asthenia (3.4%).
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), IMFINZI was
discontinued due to adverse reactions in 7% of the patients
receiving IMFINZI plus chemotherapy. Serious adverse reactions
occurred in 31% of patients receiving IMFINZI plus chemotherapy.
The most frequent serious adverse reactions reported in at least 1%
of patients were febrile neutropenia (4.5%), pneumonia (2.3%),
anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD
(1.1%). Fatal adverse reactions occurred in 4.9% of patients
receiving IMFINZI plus chemotherapy.
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse
reactions (occurring in ≥20% of patients) were fatigue, nausea,
constipation, decreased appetite, abdominal pain, rash, and
pyrexia.
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to
adverse reactions occurred in 6% of the patients receiving IMFINZI
plus chemotherapy. Serious adverse reactions occurred in 47% of
patients receiving IMFINZI plus chemotherapy. The most frequent
serious adverse reactions reported in at least 2% of patients were
cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and
acute kidney injury (2.4%). Fatal adverse reactions occurred in
3.6% of patients receiving IMFINZI plus chemotherapy. These include
ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients),
and upper gastrointestinal hemorrhage (2 patients).
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO, the most common adverse reactions
(occurring in ≥20% of patients) were rash, diarrhea, fatigue,
pruritus, musculoskeletal pain, and abdominal pain.
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO, serious adverse reactions occurred in
41% of patients. Serious adverse reactions in >1% of patients
included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia
(2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%),
and anemia (1.3%). Fatal adverse reactions occurred in 8% of
patients who received IMJUDO in combination with durvalumab,
including death (1%), hemorrhage intracranial (0.5%), cardiac
arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and
immune-mediated hepatitis (0.5%). Permanent discontinuation of
treatment regimen due to an adverse reaction occurred in 14% of
patients.
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI is indicated for the treatment of adult patients with
unresectable Stage III non-small cell lung cancer (NSCLC) whose
disease has not progressed following concurrent platinum-based
chemotherapy and radiation therapy.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing epidermal growth factor
receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)
genomic tumor aberrations.
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the
treatment of adult patients with unresectable hepatocellular
carcinoma (uHCC).
Please refer to the full Prescribing Information for important
dosage modification and management information specific to adverse
reactions.
IMPORTANT PRODUCT INFORMATION
IMFINZI is indicated for the treatment of adult patients with
unresectable Stage III non-small cell lung cancer (NSCLC) whose
disease has not progressed following concurrent platinum-based
chemotherapy and radiation therapy.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing epidermal growth factor
receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)
genomic tumor aberrations.
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the
treatment of adult patients with unresectable hepatocellular
carcinoma (uHCC).
Immune-mediated adverse reactions, which may be severe or fatal,
can occur in any organ system or tissue, including the following:
immune-mediated pneumonitis, immune-mediated colitis,
immune-mediated hepatitis, immune-mediated endocrinopathies,
immune-mediated nephritis with renal dysfunction, immune-mediated
dermatologic reactions, immune-mediated pancreatitis, and solid
organ transplant rejection. IMFINZI and IMJUDO can cause severe or
life-threatening infusion-related reactions. Fatal and other
serious complications can occur in patients who receive allogeneic
hematopoietic stem cell transplantation (HSCT) before or after
being treat with a PD-1/PD-L1 blocking antibody.
Advise women not to become pregnant or breastfeed during
treatment with IMFINZI and IMJUDO and for 3 months after the last
dose.
The most frequent serious adverse reactions reported in at least
2% of patients with unresectable, Stage III NSCLC were pneumonitis
or radiation pneumonitis (7%) and pneumonia (6%). The most frequent
serious adverse reactions reported in at least 2% of patients with
metastatic NSCLC were pneumonia (11%), anemia (5%), diarrhea
(2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile
neutropenia (2.1%). The most frequent serious adverse reactions
reported in at least 1% of patients with ES-SCLC were febrile
neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia
(1.5%), pneumonitis (1.1%) and COPD (1.1%). The most frequent
serious adverse reactions reported in at least 2% of patients with
locally advanced or metastatic BTC were cholangitis (7%), pyrexia
(3.8%), anemia (3.6%), sepsis (3.3%), and acute kidney injury
(2.4%). Serious adverse reactions in >1% of patients with uHCC
included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia
(2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%),
and anemia (1.3%).
Most common adverse reactions (≥20% of patients with
unresectable, Stage III NSCLC) were cough, fatigue,
pneumonitis/radiation pneumonitis, upper respiratory tract
infections, dyspnea, and rash. The most common adverse reactions
(≥20% of patients with metastatic NSCLC) were nausea (42%), fatigue
(36%), musculoskeletal pain (29%), decreased appetite (28%), rash
(27%), and diarrhea (22%). Most common adverse reactions (≥20% of
patients with ES-SCLC) were nausea, fatigue/asthenia, alopecia. The
most common adverse reactions (≥20% of adult patients with locally
advanced or metastatic BTC) were fatigue, nausea, constipation,
decreased appetite, abdominal pain, rash, and pyrexia. The most
common adverse reactions (occurring in ≥20% of patients with uHCC)
were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and
abdominal pain.
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Please refer to the full Prescribing Information for important
dosage modification and management information specific to adverse
reactions.
Notes
Ovarian cancer
Ovarian cancer is one of the most common gynecologic cancers and
is the eighth most common cancer in women worldwide with more than
314,000 new patients diagnosed in 2020 and over 207,000 deaths.
This number is expected to rise by almost 42% by 2040 to over
445,000 newly diagnosed patients and 314,000 deaths.1,2,3
Over two-thirds of patients are diagnosed with advanced disease,
which can progress quickly, often within two years, diminishing
their quality of life despite treatment. Unfortunately, 50-70% of
patients with advanced disease die within five years.4-7 Outcomes
are generally worse in patients with homologous recombination
deficiency (HRD)-negative disease, where survival at five years is
approximately 30%.5,8
DUO-O
DUO-O is a Phase III randomized, double-blind,
placebo-controlled, multi-center trial to evaluate the efficacy and
safety of IMFINZI in combination with platinum-based chemotherapy
and bevacizumab followed by maintenance treatment with IMFINZI and
bevacizumab with or without LYNPARZA in newly diagnosed patients
with advanced ovarian cancer without tumor BRCA mutations.
Patients were randomized 1:1:1 to: Arm 1 (control), induction
therapy with platinum-based chemotherapy in combination with
bevacizumab and placebo followed by maintenance treatment with
bevacizumab plus placebo; Arm 2, induction therapy with
platinum-based chemotherapy in combination with bevacizumab and
IMFINZI followed by maintenance IMFINZI and bevacizumab plus
placebo; or Arm 3, induction therapy with platinum-based
chemotherapy in combination with bevacizumab and IMFINZI followed
by maintenance IMFINZI and bevacizumab plus LYNPARZA. In all arms,
platinum-based chemotherapy was administered every 3 weeks (q3w)
for up to 6 cycles, bevacizumab was administered q3w for up to 15
months, IMFINZI or placebo was administered q3w for up to 24
months, and LYNPARZA or placebo was administered twice daily for up
to 24 months.
The primary endpoint of the trial is progression-free survival
(PFS) as assessed by investigator for Arm 3 compared to Arm 1
(control) in the overall trial population which included patients
without tumor BRCA mutations and in the subset of these patients
with homologous recombination deficiency (HRD)-positive disease.
Key secondary endpoints include PFS as assessed by investigator in
Arm 2 compared to control, as well as comparisons for overall
survival (OS). DUO-O enrolled over 1200 patients across all
treatment arms at 179 study locations. For more information about
the trial, visit ClinicalTrials.gov.
IMFINZI
IMFINZI (durvalumab) is a human monoclonal antibody that binds
to the PD-L1 protein and blocks the interaction of PD-L1 with the
PD-1 and CD80 proteins, countering the tumor’s immune-evading
tactics and releasing the inhibition of immune responses.
IMFINZI is the only approved immunotherapy and the global
standard of care in the curative-intent setting of unresectable,
Stage III non-small cell lung cancer (NSCLC) in patients whose
disease has not progressed after chemoradiation therapy based on
the PACIFIC Phase III trial. IMFINZI is also approved in the US,
EU, Japan, China and many other countries around the world for the
treatment of extensive-stage small cell lung cancer (SCLC) based on
the CASPIAN Phase III trial. Additionally, IMFINZI is approved in
combination with a short course of IMJUDO® (tremelimumab-actl) and
chemotherapy for the treatment of metastatic NSCLC in the US, EU
and Japan based on the POSEIDON Phase III trial.
In addition to its indications in lung cancer, IMFINZI is also
approved in combination with chemotherapy in locally advanced or
metastatic biliary tract cancer in the US, EU, Japan and several
other countries; in combination with IMJUDO in unresectable
hepatocellular carcinoma in the US, EU and Japan; and in previously
treated patients with advanced bladder cancer in a small number of
countries.
Since the first approval in May 2017, more than 200,000 patients
have been treated with IMFINZI. As part of a broad development
program, IMFINZI is being tested as a single treatment and in
combinations with other anti-cancer treatments for patients with
SCLC, NSCLC, bladder cancer, several gastrointestinal cancers and
other solid tumors.
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 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
deficiency (HRD)-positive advanced ovarian cancer, respectively;
for germline BRCA-mutated (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; in
combination with abiraterone for the treatment of metastatic
castration-resistant prostate cancer (mCRPC) in whom chemotherapy
is not clinically indicated (in the EU) and as monotherapy in HRR
gene-mutated mCRPC in patients who have progressed on prior NHA
treatment (BRCAm only in the EU and Japan). In China, LYNPARZA is
approved for the treatment of BRCA-mutated mCRPC, as a 1st-line
maintenance therapy in BRCA-mutated advanced ovarian cancer as well
as 1st-line maintenance treatment with bevacizumab for HRD-positive
advanced ovarian cancer.
LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck & Co., Inc., known as MSD outside the US
and Canada, has been used to treat over 75,000 patients worldwide.
The companies develop LYNPARZA in combination with their respective
PD-L1 and PD-1 medicines independently. LYNPARZA is the foundation
of AstraZeneca's industry-leading portfolio of potential new
medicines targeting DDR mechanisms in cancer cells.
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.
By harnessing the power of six scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response,
Antibody Drug Conjugates, Epigenetics and Cell Therapies – 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.
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. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References
- Momenimovahed Z, et al. Ovarian Cancer in the World:
Epidemiology and Risk Factors. Int J Womens Health. 2019 Apr
30;11:287-299.
- World Cancer Research Fund International. Ovarian Cancer
Statistics. Available at
https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/#:~:text=Latest%20ovarian%20cancer%20data,of%20ovarian%20cancer%20in%202020.
Accessed May 2023.
- WOCC. Global Ovarian Cancer Charter Data Briefing. Available at
https://worldovariancancercoalition.org/wp-content/uploads/2022/02/Global-Priority_Final.pdf.
Accessed May 2023.
- National Cancer Institute. Cancer Stat Facts: Ovarian Cancer.
Available at https://seer.cancer.gov/statfacts/html/ovary.html.
Accessed May 2023.
- Ray-Coquard, et al. Final Overall Survival (OS) Results From
the Phase III PAOLA-1/ENGOT-ov25 Trial Evaluating Maintenance
Olaparib (ola) Plus Bevacizumab (bev) in Patients (pts) with Newly
Diagnosed Advanced Ovarian Cancer (AOC). Presented at the European
Society of Medical Oncology Congress. Paris, France. 09 September
2022.
- Ray-Coquard I, et al. Olaparib Plus Bevacizumab as First-Line
Maintenance in Ovarian Cancer. N Engl J Med. 2019;
381:2416-2428
- González-Martín A, et al. Niraparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;
381:2391-2402
- Medical News Today. What To Know About HRD Testing For Ovarian
Cancer. Available at
https://www.medicalnewstoday.com/articles/hrd-positive-ovarian-cancer.
Accessed May 2023.
View source
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Media Inquiries Brendan McEvoy +1 302 885 2677 Jessica
McDuell +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
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