First immunotherapy regimen before and after
surgery to demonstrate statistically significant and clinically
meaningful overall survival improvement in this setting
Positive results from the NIAGARA Phase III trial showed
AstraZeneca’s IMFINZI® (durvalumab) in combination with
chemotherapy demonstrated a statistically significant and
clinically meaningful improvement in the primary endpoint of
event-free survival (EFS) and the key secondary endpoint of overall
survival (OS) versus neoadjuvant chemotherapy for patients with
muscle-invasive bladder cancer (MIBC). Patients were treated with
IMFINZI in combination with neoadjuvant chemotherapy before radical
cystectomy (surgery to remove the bladder) followed by IMFINZI as
adjuvant monotherapy.
These results will be presented today during a Presidential
Symposium at the 2024 European Society for Medical Oncology (ESMO)
Congress in Barcelona, Spain (abstract #LBA5) and simultaneously
published in The New England Journal of Medicine.
In a planned interim analysis, patients treated with the IMFINZI
perioperative regimen showed a 32% reduction in the risk of disease
progression, recurrence, not undergoing surgery, or death versus
the comparator arm (based on EFS hazard ratio [HR] of 0.68; 95%
confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median
EFS was not yet reached for IMFINZI arm versus 46.1 months for the
comparator arm. An estimated 67.8% of patients treated with the
IMFINZI regimen were event free at two years compared to 59.8% in
the comparator arm.
Results from the key secondary endpoint of OS showed the IMFINZI
perioperative regimen reduced the risk of death by 25% versus
neoadjuvant chemotherapy with radical cystectomy (based on OS HR of
0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet
reached for either arm. An estimated 82.2% of patients treated with
the IMFINZI regimen were alive at two years compared to 75.2% in
the comparator arm.
Professor Thomas Powles, MD, Director of Barts Cancer Centre
(QMUL), London, UK, and principal investigator in the NIAGARA
trial, said: “Neoadjuvant chemotherapy with bladder removal has
been the mainstay of treatment for patients with muscle-invasive
bladder cancer for nearly twenty years; however, half of patients
still go to suffer a devastating recurrence. Adding durvalumab
before and after surgery significantly reduced the chance of
recurrence and extended survival, a significant advance with the
potential to transform the standard of care for these patients who
desperately need better outcomes.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The NIAGARA data showed compelling improvements
in both event-free survival and overall survival, with more than 80
percent of patients treated with the IMFINZI perioperative regimen
alive at two years. This is the first immunotherapy regimen to
significantly extend overall survival in muscle-invasive bladder
cancer, and it further validates our strategy to move cancer
treatment as early as possible to maximize benefit for
patients.”
Summary of results: NIAGARA
IMFINZI-based regimen
(n=533)
Neoadjuvant
chemotherapy
(n=530)
EFS
Number of patients with event (%)
187 (35.1)
246 (46.4)
Median EFS (95% CI) (in months)
NR (NR-NR)
46.1 (32.2-NR)
HR (95% CI)
0.68
(0.56-0.82)
p-value
<0.0001
EFS rate at 12 months (%)
76.0
69.9
EFS rate at 24 months (%)
67.8
59.8
OS
Number of deaths, n (%)
136 (25.5)
169 (31.9)
HR (95% CI)
0.75
(0.59-0.93)
Stratified log-rank p-value
0.0106
OS rate at 12 months (%)
89.5
86.5
OS rate at 24 months (%)
82.2
75.2
i With the observed number of events, the
boundary for declaring statistical significance was 0.04123 for a
4.9% overall 2-sided alpha
ii With the observed number of events, the
boundary for declaring statistical significance was 0.01543 for a
4.9% overall 2-sided alpha. Data cutoff 24 Apr 2024.
iii Unplanned pCR re-analysis (DCO Apr
24), including 59 samples omitted from formal pCR analysis.
NR, not reached
IMFINZI was generally well tolerated and no new safety signals
were observed in the neoadjuvant and adjuvant settings. Further,
adding IMFINZI to neoadjuvant chemotherapy was consistent with the
known profile for this combination and did not compromise patients’
ability to complete surgery compared to neoadjuvant chemotherapy
alone. Grade 3 and 4 adverse events due to any cause occurred in
69% of patients treated with IMFINZI and 68% of patients treated
with neoadjuvant chemotherapy.
In addition to NIAGARA, IMFINZI is also being tested across
early- and late-stage bladder cancer in various treatment
combinations, including in non-muscle invasive disease (POTOMAC),
patients with MIBC who are cisplatin-ineligible or refusing
cisplatin (VOLGA) and locally advanced or metastatic disease
(NILE).
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 given 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 with IMJUDO and platinum-based chemotherapy can cause
immune-mediated colitis, which may be fatal. 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.
- 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.
- IMFINZI with Carboplatin and Paclitaxel
- Immune-mediated hypothyroidism occurred in 14% (34/235) of
patients receiving IMFINZI in combination with carboplatin and
paclitaxel.
- 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),
has 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 and
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, other transplant (including corneal graft)
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 Unresectable Stage III NSCLC
- 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.
Resectable NSCLC
- In patients with resectable NSCLC in the AEGEAN study, the most
common adverse reactions (occurring in ≥20% of patients) were
anemia, nausea, constipation, fatigue, musculoskeletal pain, and
rash.
- In patients with resectable NSCLC in the neoadjuvant phase of
the AEGEAN study receiving IMFINZI in combination with
platinum-containing chemotherapy (n=401), permanent discontinuation
of IMFINZI due to an adverse reaction occurred in 6.7% of patients.
Serious adverse reactions occurred in 21% of patients. The most
frequent (≥1%) serious adverse reactions were pneumonia (2.7%),
anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%),
neutropenia (1%), and acute kidney injury (1%). Fatal adverse
reactions occurred in 2% of patients, including death due to
COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%),
decreased appetite (0.2%), hemoptysis (0.2%), and death not
otherwise specified (0.2%). Of the 401 IMFINZI treated patients who
received neoadjuvant treatment and 398 placebo-treated patients who
received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4),
respectively, did not receive surgery due to adverse
reactions.
- In patients with resectable NSCLC in the adjuvant phase of the
AEGEAN study receiving IMFINZI as a single agent (n=265), permanent
discontinuation of IMFINZI due to an adverse reaction occurred in
8% of patients. Serious adverse reactions occurred in 13% of
patients. The most frequent serious adverse reactions reported in
>1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and
COVID-19 (1.1%). Four fatal adverse reactions occurred during the
adjuvant phase of the study, including COVID-19 pneumonia,
pneumonia aspiration, interstitial lung disease and aortic
aneurysm.
Metastatic NSCLC
- 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.
Extensive-stage Small Cell Lung Cancer
- 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.
Locally Advanced or Metastatic Biliary Tract Cancers
- 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 (42%),
nausea (40%), constipation (32%), decreased appetite (26%),
abdominal pain (24%), rash (23%), and pyrexia (20%).
- 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).
Unresectable Hepatocellular Carcinoma
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), the most common adverse
reactions (occurring in ≥20% of patients) were rash (32%), diarrhea
(27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%),
and abdominal pain (20%).
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), 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 IMFINZI and IMJUDO, 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.
Primary advanced or Recurrent dMMR Endometrial Cancer
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), the most common adverse reactions, including laboratory
abnormalities (occurring in >20% of patients) were peripheral
neuropathy (61%), musculoskeletal pain (59%), nausea (59%),
alopecia (52%), fatigue (41%), abdominal pain (39%), constipation
(39%), rash (39%), decreased magnesium (36%), increased ALT (32%),
increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%),
decreased potassium (25%), dyspnea (25%), headache (23%), increased
alkaline phosphatase (20%), and decreased appetite (18%). The most
common Grade 3 or 4 adverse reactions (≥3%) were constipation
(4.5%) and fatigue (4.5%).
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), permanent discontinuation of IMFINZI due to adverse
reactions occurred in 11% of patients. Serious adverse reactions
occurred in 30% of patients who received IMFINZI with carboplatin
and paclitaxel; the most common serious adverse reactions (≥4%)
were constipation (4.5%) and rash (4.5%).
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI, as a single agent, 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 platinum-containing chemotherapy as
neoadjuvant treatment, followed by IMFINZI continued as a single
agent as adjuvant treatment after surgery, is indicated for the
treatment of adult patients with resectable (tumors ≥4 cm and/or
node positive) NSCLC and no known epidermal growth factor receptor
(EGFR) mutations or anaplastic lymphoma kinase (ALK)
rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing EGFR mutations or 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).
IMFINZI in combination with carboplatin and paclitaxel followed
by IMFINZI as a single agent is indicated for the treatment of
adult patients with primary advanced or recurrent endometrial
cancer that is mismatch repair deficient (dMMR).
Please see additional Important Safety Information throughout
and Full Prescribing Information including Medication Guide for
IMFINZI and IMJUDO.
You may report side effects related to AstraZeneca products.
Notes
Muscle-invasive bladder cancer Bladder cancer is the 9th
most common cancer in the world, with more than 614,000 patients
diagnosed each year. The most common type of bladder cancer is
urothelial carcinoma, which begins in the urothelial cells of the
urinary tract.
MIBC, named for its growth into the muscle wall of the bladder,
accounts for about a quarter of all bladder cancer cases. In the
MIBC setting, approximately 117,000 patients are treated with
current standard of care. Standard treatment includes neoadjuvant
chemotherapy and radical cystectomy. However, even after
cystectomy, patients experience high rates of recurrence and a poor
prognosis. Approximately 50% of patients who undergo bladder
removal surgery experience disease recurrence. Treatment options
that prevent disease recurrence after surgery are critically
needed.
NIAGARA NIAGARA is a randomized, open-label,
multi-center, global Phase III trial evaluating IMFINZI as
treatment for patients with MIBC before and after radical
cystectomy. In the trial, 1,063 patients were randomized to receive
IMFINZI plus chemotherapy or chemotherapy alone prior to
cystectomy, followed by IMFINZI or no further treatment after
surgery.
The trial is being conducted at 192 centers across 22 countries
including in the US, Canada, Europe, Australia and Asia. Its dual
primary endpoints are EFS, defined as the time from treatment
randomization to an event like tumor recurrence or progression and
pathologic complete response. Key secondary endpoints are OS and
safety.
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 chemoradiotherapy. Additionally,
IMFINZI is approved as a perioperative treatment in combination
with neoadjuvant chemotherapy in resectable NSCLC, for the
treatment of extensive-stage small cell lung cancer (SCLC) and in
combination with a short course of IMJUDO® (tremelimumab-actl) and
chemotherapy for the treatment of metastatic NSCLCs.
In addition to its indications in lung cancers, IMFINZI is
approved in combination with chemotherapy (gemcitabine plus
cisplatin) in locally advanced or metastatic biliary tract cancer
and in combination with IMJUDO in unresectable hepatocellular
carcinoma (HCC). IMFINZI is also approved as a monotherapy in
unresectable HCC in Japan and the EU. IMFINZI is also approved in
combination with chemotherapy (carboplatin and paclitaxel) followed
by IMFINZI monotherapy in primary advanced or recurrent endometrial
cancer that is mismatch repair deficient (dMMR) in the US. In the
EU, IMFINZI plus chemotherapy followed by olaparib and IMFINZI is
approved for patients with mismatch repair proficient disease
advanced or recurrent endometrial cancer, and IMFINZI plus
chemotherapy followed by IMFINZI alone is approved for patients
with dMMR disease.
Since the first approval in May 2017, more than 220,000
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, breast cancer, bladder cancer, several
gastrointestinal and gynaecologic cancers, and other solid
tumors.
AstraZeneca in immuno-oncology (IO) AstraZeneca is a
pioneer in introducing the concept of immunotherapy into dedicated
clinical areas of high unmet medical need. The Company has a
comprehensive and diverse IO portfolio and pipeline anchored in
immunotherapies designed to overcome evasion of the anti-tumor
immune response and stimulate the body’s immune system to attack
tumors.
AstraZeneca strives to redefine cancer care and help transform
outcomes for patients with IMFINZI a monotherapy and in combination
with IMJUDO as well as other novel immunotherapies and modalities.
The Company is also investigating next-generation immunotherapies
like bispecific antibodies and therapeutics that harness different
aspects of immunity to target cancer, including cell therapy and T
cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to
bring IO-based therapies that deliver long-term survival to new
settings across a wide range of cancer types. The Company is
focused on exploring novel combination approaches to help prevent
treatment resistance and drive longer immune responses. With an
extensive clinical program, the Company also champions the use of
IO treatment in earlier disease stages, where there is the greatest
potential for cure.
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.
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
125 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 social media
@AstraZeneca.
References
- World Health Organization. International Agency for Research on
Cancer. Bladder Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf.
Accessed September 2024.
- American Cancer Society. What Is Bladder Cancer? Available at:
https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html.
Accessed September 2024.
- Burger M, et al. Epidemiology and Risk Factors of Urothelial
Bladder Cancer. Eur Urol. 2013;63(2):234-241.
- National Collaborating Centre for Cancer. Bladder Cancer:
Diagnosis and Management. London: National Institute for Health and
Care Excellence (NICE). Available at:
https://www.ncbi.nlm.nih.gov/books/NBK356289. Accessed September
2024.
- Cerner CancerMPact database. Accessed September 2024. Reflects
epidemiology estimates across G8 countries (US, EU, Japan,
China).
- Witjes JA, et al. EAU Guidelines on Muscle-invasive and
Metastatic Bladder Cancer. Eur Urol. 2021;1-94.
US-93498 Last Updated 9/24
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