IMFINZI® (Durvalumab) is the Only Immunotherapy to Demonstrate Overall Survival at Three Years in Unresectable, Stage III Non-Small Cell Lung Cancer
June 2, 2019
Data presented at ASCO 2019 showed 57% of patients alive at three
years vs. 43.5% on placebo
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca has presented three-year overall survival (OS) results from
the Phase III PACIFIC trial of IMFINZI® (durvalumab) in
unresectable, Stage III non-small cell lung cancer (NSCLC) during the
2019 American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago.
The latest results from this post-hoc analysis show longer-term OS
evidence in patients with unresectable, Stage III NSCLC who had not
progressed following concurrent chemoradiation therapy (CRT), a previous
standard-of-care (SoC) treatment. The OS rate was 57% at three years for
patients receiving IMFINZI vs. 43.5% for placebo following concurrent
CRT. Median OS was not yet reached with the IMFINZI arm versus
29.1 months for placebo.
Dave Fredrickson, Executive Vice President, Oncology Business said:
“These findings for IMFINZI are another example of our focus on bringing
long-term survival benefits to patients who still have a chance of being
cured. These three-year survival results further establish the PACIFIC
regimen as the standard of care for these patients, and we are
optimistic that this survival trend will continue as we move towards the
five-year landmark in this curative-intent setting.”
Results build on the primary two-year OS analysis that was published in The
New England Journal of Medicine in September 2018 and
demonstrated a significant OS benefit for treatment with IMFINZI vs.
placebo after CRT, regardless of PD-L1 expression. The primary analysis
showed IMFINZI reduced the risk of death by 32% (HR 0.68, 99.73% CI
0.47-0.997; p=0.0025).
With the additional year of follow up, the latest results for IMFINZI
showed consistent efficacy, maintaining a 31% reduction in the risk of
death vs. placebo after CRT (HR 0.69, [95% CI 0.55-0.86]).
Jhanelle Gray, MD, Director of Clinical Research in the Thoracic
Oncology Department at Moffitt Cancer Center in Tampa, Florida, and an
investigator in the PACIFIC trial, said: “In the past, patients with
unresectable, Stage III non-small cell lung cancer faced five-year
survival rates of only 15 to 30%. It is remarkable to see more than half
of the patients treated with the PACIFIC regimen alive after three
years, an important milestone in this curative-intent setting.”
IMFINZI can cause serious, potentially fatal adverse events (AEs). In
the previous two-year OS analysis, the most common adverse reactions
(greater than or equal to 20% of patients) for patients receiving
IMFINZI versus placebo were cough (35.2% vs. 25.2%), fatigue (24.0% vs.
20.5%), dyspnea (22.3% vs. 23.9%) and radiation pneumonitis (20.2% vs.
15.8%). 30.5% of patients experienced a grade 3 or 4 AE with IMFINZI vs.
26.1% with placebo, and 15.4% of patients discontinued treatment due to
AEs with IMFINZI vs. 9.8% of patients on placebo.
Building on PACIFIC
AstraZeneca has several ongoing trials focused on testing IMFINZI®
(durvalumab) in earlier stages of NSCLC (Stage I-III) and in
potentially-curative settings. The Phase III PACIFIC-2 trial design,
presented today at the ASCO Annual Meeting, is evaluating IMFINZI given
concurrently with CRT in patients with unresectable, Stage III NSCLC.
IMFINZI is approved for the treatment of unresectable, Stage III
non-small cell lung cancer in more than 45 countries, including the US,
EU and Japan, based on the Phase III PACIFIC trial. Since the first
approval in the US in February 2018, more than 20,000 patients in this
setting have been treated with IMFINZI.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab).
IMFINZI can cause serious, potentially fatal adverse reactions
including immune-mediated pneumonitis, hepatitis, colitis or diarrhea,
endocrinopathies, nephritis, rash or dermatitis,
other immune-mediated adverse reactions, infection, and infusion-related
reactions. Please refer to the full Prescribing Information for
important dosage modification and management information specific to
adverse reactions.
Immune-Mediated Pneumonitis
IMFINZI can cause immune-mediated pneumonitis, defined as requiring use
of corticosteroids. Fatal cases have been reported. Monitor patients for
signs and symptoms of pneumonitis and evaluate with radiographic imaging
when suspected. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently
discontinue for Grade 3 or 4 pneumonitis.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, pneumonitis occurred in 5% of patients, including
Grade 3 (0.8%), Grade 4 (<0.1%), and Grade 5 (0.3%) pneumonitis.
Pneumonitis led to discontinuation of IMFINZI in 1.5% of the 1889
patients. In the PACIFIC study, the incidence of pneumonitis (including
radiation pneumonitis) was 34%, including Grade 3 (3.4%) and Grade 5
(1.1%) pneumonitis in the IMFINZI arm. In the PACIFIC study, pneumonitis
led to discontinuation of IMFINZI in 6% of patients.
Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis, defined as requiring use of
corticosteroids. Fatal cases have been reported. Monitor patients for
signs and symptoms of hepatitis during and after discontinuation of
IMFINZI, including clinical chemistry monitoring. Administer
corticosteroids for Grade 2 or higher elevations of ALT, AST, and/or
total bilirubin. Withhold IMFINZI for ALT or AST greater than 3 but less
than or equal to 8 times the ULN or total bilirubin greater than 1.5 but
less than or equal to 5 times the ULN; permanently discontinue IMFINZI
for ALT or AST greater than 8 times the ULN or total bilirubin greater
than 5 times the ULN or concurrent ALT or AST greater than 3 times the
ULN and total bilirubin greater than 2 times the ULN with no other cause.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, hepatitis occurred in 12% of patients, including Grade
3 (4.4%), Grade 4 (0.4%), and Grade 5 (0.2%) hepatitis. Hepatitis led to
discontinuation of IMFINZI in 0.7% of the 1889 patients.
Immune-Mediated Colitis
IMFINZI can cause immune-mediated colitis, defined as requiring use of
corticosteroids. Administer corticosteroids for Grade 2 or greater
colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea;
permanently discontinue for Grade 3 or 4 colitis or diarrhea.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, colitis or diarrhea occurred in 18% of patients,
including Grade 3 (1.0%) and Grade 4 (0.1%) colitis. Diarrhea or colitis
led to discontinuation of IMFINZI in 0.4% of the 1889 patients.
Immune-Mediated Endocrinopathies
IMFINZI can cause immune-mediated endocrinopathies, including thyroid
disorders, adrenal insufficiency, type 1 diabetes mellitus, and
hypophysitis/hypopituitarism. Monitor patients for clinical signs
and symptoms of endocrinopathies.
-
Thyroid disorders—Monitor thyroid function prior to and
periodically during treatment. Initiate hormone replacement therapy or
medical management of hyperthyroidism as clinically indicated.
Withhold IMFINZI for Grades 2–4 hyperthyroidism, until clinically
stable. Continue IMFINZI for hypothyroidism. In clinical studies
enrolling 1889 patients with various cancers who received
IMFINZI, hypothyroidism occurred in 11% of patients, while
hyperthyroidism occurred in 7% of patients. Thyroiditis occurred in
0.9% of patients, including Grade 3 (<0.1%). Hypothyroidism was
preceded by thyroiditis or hyperthyroidism in 25% of patients. -
Adrenal insufficiency—Administer corticosteroids as clinically
indicated and withhold IMFINZI until clinically stable for Grade 2 or
higher adrenal insufficiency. In clinical studies enrolling 1889
patients with various cancers who received IMFINZI, adrenal
insufficiency occurred in 0.7% of patients, including Grade 3 (<0.1%)
adrenal insufficiency. -
Type 1 diabetes mellitus—Initiate treatment with insulin as
clinically indicated. Withhold IMFINZI for Grades 2–4 type 1 diabetes
mellitus, until clinically stable. In clinical studies enrolling 1889
patients with various cancers who received IMFINZI, type 1 diabetes
mellitus occurred in <0.1% of patients. -
Hypophysitis—Administer corticosteroids and hormone replacement
as clinically indicated and withhold IMFINZI until clinically stable
for Grade 2 or higher hypophysitis. Hypopituitarism leading to adrenal
insufficiency and diabetes insipidus occurred in <0.1% of 1889
patients with various cancers who received IMFINZI.
Immune-Mediated Nephritis
IMFINZI can cause immune-mediated nephritis, defined as evidence of
renal dysfunction requiring use of corticosteroids. Fatal cases have
occurred. Monitor patients for abnormal renal function tests prior to
and periodically during treatment with IMFINZI. Administer
corticosteroids as clinically indicated. Withhold IMFINZI for creatinine
greater than 1.5 to 3 times the ULN; permanently discontinue IMFINZI and
administer corticosteroids in patients with creatinine greater than 3
times the ULN.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, nephritis (reported as any of the following: increased
creatinine or urea, acute kidney injury, renal failure, decreased
glomerular filtration rate, tubulointerstitial nephritis, decreased
creatinine clearance, glomerulonephritis, and nephritis) occurred in
6.3% of the patients including Grade 3 (1.1%), Grade 4 (0.2%), and Grade
5 (0.1%) nephritis. IMFINZI was discontinued in 0.3% of the 1889
patients.
Immune-Mediated Dermatologic Reactions
IMFINZI can cause immune-mediated rash. Bullous dermatitis and Stevens
Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) have occurred
with other products in this class. Administer corticosteroids for Grade
2 rash or dermatitis lasting for more than 1 week or for Grade 3 or 4
rash or dermatitis. Withhold IMFINZI for Grade 2 rash or dermatitis
lasting longer than 1 week or Grade 3 rash or dermatitis; permanently
discontinue IMFINZI in patients with Grade 4 rash or dermatitis.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, 26% of patients developed rash or dermatitis and 0.4%
of the patients developed vitiligo. Rash or dermatitis led to
discontinuation of IMFINZI in 0.1% of the 1889 patients.
Other Immune-Mediated Adverse Reactions
IMFINZI can cause severe and fatal immune-mediated adverse reactions.
These immune-mediated reactions may involve any organ system. While
immune-mediated reactions usually manifest during treatment with
IMFINZI, immune-mediated adverse reactions can also manifest after
discontinuation of IMFINZI. For suspected immune-mediated adverse
reactions, exclude other causes and initiate corticosteroids as
clinically indicated. Withhold IMFINZI for Grade 3 immune-mediated
adverse reactions, unless clinical judgment indicates discontinuation;
permanently discontinue IMFINZI for Grade 4 adverse reactions.
The following clinically significant, immune-mediated adverse reactions
occurred at an incidence of less than 1% each in 1889 patients who
received IMFINZI: aseptic meningitis, hemolytic anemia, immune
thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory
toxicity, including uveitis and keratitis. Additional clinically
significant immune-mediated adverse reactions have been seen with other
products in this class (see Warnings and Precautions Section 5.7 of
IMFINZI full Prescribing Information).
Infection
IMFINZI can cause serious infections, including fatal cases. Monitor
patients for signs and symptoms of infection and treat as clinically
indicated. Withhold IMFINZI for Grade 3 or 4 infection, until clinically
stable.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, infections occurred in 43% of patients, including
Grade 3 (8%), Grade 4 (1.9%), and Grade 5 (1.0%). In patients with Stage
III NSCLC in the PACIFIC study, the most common Grade 3 or higher
infection was pneumonia, which occurred in 5% of patients.
Infusion-Related Reactions
IMFINZI can cause severe or life-threatening infusion-related reactions.
Monitor patients for signs and symptoms of an infusion-related reaction.
Interrupt or slow the rate of infusion for Grades 1–2 infusion-related
reactions; permanently discontinue for Grades 3–4 infusion-related
reactions.
In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, infusion-related reactions occurred in 2.2% of
patients, including Grade 3 (0.3%).
Embryo-Fetal Toxicity
Based on its mechanism of action and data from animal studies, IMFINZI
can cause fetal harm when administered to a pregnant woman. There are no
data on the use of IMFINZI in pregnant women. Advise pregnant women of
the potential risk to a fetus and advise women of reproductive potential
to use effective contraception during treatment and for at least 3
months after the last dose of IMFINZI.
Lactation
There is no information regarding the presence of IMFINZI in human milk;
however, because of the potential for adverse reactions in breastfed
infants from IMFINZI, advise women not to breastfeed during treatment
and for at least 3 months after the last dose.
Most Common Adverse Reactions
-
In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475),
the most common adverse reactions (≥20% of patients) 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 reaction (≥3%) was pneumonia (7%). -
In patients with Stage III NSCLC in the PACIFIC study (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% of patients) 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.
The safety and effectiveness of IMFINZI have not been established in
pediatric patients.
Indication
IMFINZI is indicated for the treatment of patients with unresectable
Stage III non-small cell lung cancer (NSCLC) whose disease has not
progressed following concurrent platinum-based chemotherapy and
radiation therapy.
Please see complete Prescribing
Information, including Medication Guide.
NOTES TO EDITORS
About PACIFIC
The PACIFIC trial is a Phase III, randomized, double-blinded,
placebo-controlled, multi-center trial of IMFINZI®
(durvalumab) as treatment in ”all-comer” patients (i.e., regardless of
PD-L1 status) with unresectable Stage III NSCLC whose disease has not
progressed following platinum-based chemotherapy concurrent with
radiation therapy (CRT).
The trial is being conducted in 235 centers across 26 countries
involving 713 patients. The primary endpoints of the trial are
progression-free survival (PFS) and overall survival (OS), and secondary
endpoints include landmark PFS and OS, overall response rate (ORR) and
duration of response (DoR).
About Stage III NSCLC
Stage III (locally advanced) non-small cell lung cancer (NSCLC) is
commonly divided into three sub-categories (IIIA, IIIB and IIIC),
defined by how much the cancer has spread locally and the possibility of
surgery. Stage III disease is different from Stage IV disease, when the
cancer has spread (metastasized) to distant organs, as Stage III is
currently treated with curative intent.
Approximately one in four patients with NSCLC in the United States
present with Stage III disease, which is estimated to affect over 43,000
patients. The majority of Stage III NSCLC patients are diagnosed with
unresectable tumors. Until recently, the standard of care beyond CRT was
active surveillance to monitor for progression as there had been no FDA
approved treatments following CRT.
About IMFINZI® (durvalumab)
IMFINZI® (durvalumab) is a human monoclonal antibody that
binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80,
countering the tumor’s immune-evading tactics and releasing the
inhibition of immune responses.
IMFINZI is approved for unresectable, Stage III NSCLC in more
than 45 countries including the US, EU, and Japan based on the Phase III
PACIFIC trial.
As part of a broad development program, IMFINZI is also being
tested as a monotherapy and in combination with tremelimumab, an
investigational anti-CTLA4 monoclonal antibody and potential new
medicine, as a treatment for patients with NSCLC, small cell lung cancer
(SCLC), bladder cancer, head and neck cancer, liver cancer, cervical
cancer, biliary tract cancer and other solid tumors.
About AstraZeneca Support Programs
AstraZeneca strives to ensure that appropriate patients and their
oncologists have access to IMFINZI and relevant support resources. These
include educational resources, an Oncology Nurse Educator program and
affordability and reimbursement programs, such as Access
360™.
Additionally, AstraZeneca has launched Lighthouse,
a program that provides support to patients during any immune-mediated
adverse events they may encounter during treatment, through medically
trained Lighthouse Advocates. The program aims to make patients’
treatment experience as comfortable as possible. Find out more about
Lighthouse at LighthouseProgram.com or call 1-855-LHOUSE1
(1-855-546-8731).
About AstraZeneca in Lung Cancer
AstraZeneca has a comprehensive portfolio of approved and
investigational medicines in late-stage clinical development for the
treatment of different forms of lung cancer spanning several stages of
disease and lines of therapy. We aim to address the unmet needs of
patients with EGFR-mutated tumors as a genetic driver of disease, which
occur in approximately 7-23% of patients in Western populations, and
30-40% of Asian patients, with our approved medicine TAGRISSO®
and ongoing Phase III trials FLAURA, ADAURA and LAURA, as well as the
Phase II exploratory combination trials SAVANNAH and ORCHARD.
Our extensive late-stage Immuno-Oncology program focuses on 75-80% of
patients with lung cancer without a known genetic mutation. IMFINZI, an
anti-PD-L1 antibody, is in development as monotherapy (Phase III trials
ADJUVANT BR.31, PACIFIC-4, PACIFIC-5 and PEARL) and in combination with
tremelimumab and/or chemotherapy (AEGEAN, PACIFIC-2, NEPTUNE, POSEION,
ADRIATIC and CASPIAN Phase III trials).
About AstraZeneca’s Approach to Immuno-Oncology (IO)
Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the
body’s immune system to attack tumors. At AstraZeneca, our IO portfolio
is anchored by immunotherapies that have been designed to overcome
anti-tumor immune suppression. We believe that IO-based therapies will
offer the potential for life-changing cancer treatments for the clear
majority of patients.
We are pursuing a comprehensive clinical trial program that includes
IMFINZI (anti-PD-L1) as monotherapy and in combination with tremelimumab
(anti-CTLA-4) in multiple tumor types, stages of disease, and lines of
therapy. In addition, the ability to combine our IO portfolio with
small, targeted molecules from across our Oncology pipeline, and from
our research partners, may provide new treatment options across a broad
range of tumors.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly-growing portfolio of new medicines that has the potential to
transform patients’ lives and the Company’s future. With at least six
new medicines to be launched between 2014 and 2020, and a broad pipeline
of small molecules and biologics in development, we are committed to
advance Oncology as a key growth driver for AstraZeneca focused on lung,
ovarian, breast and blood cancers. In addition to our core capabilities,
we actively pursue innovative partnerships and investments that
accelerate the delivery of our strategy as illustrated by our investment
in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalized
combinations, AstraZeneca has the vision to redefine cancer treatment
and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in three
therapy areas – Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. 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.
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