Approval based on FLAURA2 results which
showed TAGRISSO plus chemotherapy extended median progression-free
survival by nearly 9 months vs. standard of care
AstraZeneca’s TAGRISSO® (osimertinib) with the addition of
chemotherapy has been approved in the US for the treatment of adult
patients with locally advanced or metastatic epidermal growth
factor receptor-mutated (EGFRm) non-small cell lung cancer
(NSCLC).
The approval following a Priority Review by the Food and Drug
Administration (FDA) was based on the results from the FLAURA2
Phase III trial published in The New England Journal of Medicine.
TAGRISSO with the addition of chemotherapy reduced the risk of
disease progression or death by 38% compared to TAGRISSO
monotherapy which is the 1st-line global standard of care (hazard
ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79;
p<0.0001). Median progression-free survival (PFS) by
investigator assessment was 25.5 months for patients treated with
TAGRISSO plus chemotherapy, an 8.8-month improvement versus
TAGRISSO monotherapy (16.7 months).
PFS results from blinded independent central review (BICR) were
consistent with the results by investigator assessment, showing
29.4 months median PFS with TAGRISSO plus chemotherapy, a 9.5-month
improvement over TAGRISSO monotherapy (19.9 months) (HR 0.62; 95%
CI 0.48-0.80; p=0.0002).
Each year in the US, there are over 200,000 people diagnosed
with lung cancer, and 80-85% of these patients are diagnosed with
NSCLC, the most common form of lung cancer.1-3 Approximately 70% of
people are diagnosed with advanced NSCLC.4 Additionally, about 15%
of NSCLC patients in the US have an EGFR mutation.5
Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer
Institute and principal investigator for the trial, said: “This
approval based on the unprecedented data from FLAURA2 brings a
critical new treatment option to patients with advanced
EGFR-mutated non-small cell lung cancer. Now, with the choice of
two highly effective osimertinib-based options, physicians can
better tailor treatment to an individual’s needs and help ensure
the best possible outcome for each patient.”
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “This important new treatment option can
delay disease progression by nearly nine additional months,
establishing a new benchmark with the longest reported
progression-free survival benefit in the 1st-line advanced setting.
This approval reinforces TAGRISSO as the backbone of EGFR-mutated
lung cancer treatment either as monotherapy or in combination with
chemotherapy. This news is especially important for those with a
poorer prognosis, including patients whose cancer has spread to the
brain and those with L858R mutations.”
Laurie Ambrose, President and CEO, GO2 for Lung Cancer, said:
“We are so excited to see this continued progress advancing more
personalized treatment options for our community. The more we can
target the right treatments for the right people at the right time,
the better outcomes will be for our community – a goal we all
collectively share.”
Results from a prespecified exploratory analysis of patients in
the FLAURA2 trial with brain metastases at baseline showed TAGRISSO
plus chemotherapy reduced the risk of central nervous system (CNS)
disease progression or death by 42% compared to TAGRISSO alone (HR
0.58; 95% CI 0.33-1.01) as assessed by BICR. With two years of
follow up, 74% of patients treated with TAGRISSO plus chemotherapy
had not experienced CNS disease progression or death versus 54% of
patients treated with TAGRISSO monotherapy.
While the overall survival (OS) results remained immature at the
second interim analysis (41% maturity), no trend towards a
detriment was observed (HR 0.75; 95% CI 0.57-0.97). The trial
continues to assess OS as a key secondary endpoint.
The safety profile of TAGRISSO with the addition of chemotherapy
was generally manageable and consistent with the established
profiles of the individual medicines. Adverse event (AE) rates were
higher in the TAGRISSO plus chemotherapy arm, driven by
well-characterized chemotherapy-related AEs. Discontinuation rates
for TAGRISSO due to AEs were low in both arms of the trial (11% for
TAGRISSO plus chemotherapy and 6% for monotherapy).
In December 2023, TAGRISSO with the addition of chemotherapy was
added to the NCCN Clinical Practical Guidelines in Oncology (NCCN
Guidelines®) as a NCCN Category 1 Other Recommended regimen for
patients with NSCLC whose tumors have EGFR exon 19 deletion or exon
21 L858R mutations based on the data from FLAURA2.6
The US regulatory submission was reviewed under Project Orbis,
which provides a framework for concurrent submission and review of
oncology medicines among participating international partners. As
part of Project Orbis, TAGRISSO in combination with chemotherapy is
also under review by regulatory authorities in Australia, Canada,
and Switzerland. Regulatory applications are also under review in
several other countries based on the FLAURA2 results.
TAGRISSO is approved as monotherapy in more than 100 countries
including in the US, EU, China and Japan. Approved indications
include for 1st-line treatment of patients with locally advanced or
metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M
mutation-positive NSCLC, and adjuvant treatment of early-stage
EGFRm NSCLC. Regulatory applications are under review in several
countries based on the FLAURA2 results.
As part of AstraZeneca’s ongoing commitment to treating patients
as early as possible in lung cancer, TAGRISSO is also being
investigated in the neoadjuvant setting in the NeoADAURA Phase III
trial with results expected later this year, and in the early-stage
adjuvant resectable setting in the ADAURA2 Phase III trial.
IMPORTANT SAFETY INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 4% of
the 1813 TAGRISSO-treated patients; 0.4% of cases were fatal. In
the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276
patients who received TAGRISSO in combination with pemetrexed and
platinum-based chemotherapy; 0.4% of cases were fatal. Withhold
TAGRISSO and promptly investigate for ILD in patients who present
with worsening of respiratory symptoms which may be indicative of
ILD (eg, dyspnea, cough and fever). Permanently discontinue
TAGRISSO if ILD/pneumonitis is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurs in
TAGRISSO-treated patients. Of the 1813 TAGRISSO monotherapy-treated
patients in clinical trials, 1.1% were found to have a QTc >500
msec, and 4.3% of patients had an increase from baseline QTc >60
msec. Of the 276 patients treated with TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy in the FLAURA2 study,
1.8% were found to have a QTc >500 msec, and 10.5% of patients
had an increase from baseline QTc >60 msec. No QTc-related
arrhythmias were reported. Conduct periodic monitoring with ECGs
and electrolytes in patients with congenital long QTc syndrome,
congestive heart failure, electrolyte abnormalities, or those who
are taking medications known to prolong the QTc interval.
Permanently discontinue TAGRISSO in patients who develop QTc
interval prolongation with signs/symptoms of life-threatening
arrhythmia
- Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated
patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2
study, cardiomyopathy occurred in 9% of the 276 patients who
received TAGRISSO in combination with pemetrexed and platinum-based
chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in
left ventricular ejection fraction (LVEF) ≥10% from baseline and to
<50% LVEF occurred in 4.2% of 1557 patients who had baseline and
at least one follow-up LVEF assessment. In the ADAURA study, 1.5%
(5/325) of TAGRISSO-treated patients experienced LVEF decreases
≥10% from baseline and a drop to <50%. In the FLAURA2 study, 8%
(21/262) of patients treated with TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy, who had baseline and at
least one follow-up LVEF assessment, experienced LVEF decreases
≥10% and a drop to less than 50%. For patients receiving TAGRISSO
monotherapy, conduct cardiac monitoring in patients with cardiac
risk factors, including assessment of LVEF at baseline and during
treatment. For patients receiving TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy, conduct cardiac
monitoring in all patients, including assessment of LVEF at
baseline and during treatment. Assess LVEF in patients who develop
relevant cardiac signs or symptoms during treatment. For
symptomatic congestive heart failure, permanently discontinue
TAGRISSO
- Keratitis was reported in 0.6% of 1813 patients treated with
TAGRISSO monotherapy in clinical trials. Promptly refer patients
with signs and symptoms suggestive of keratitis (such as eye
inflammation, lacrimation, light sensitivity, blurred vision, eye
pain and/or red eye) to an ophthalmologist
- Postmarketing cases consistent with erythema multiforme major
(EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) have been reported in patients receiving TAGRISSO.
Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently
discontinue if confirmed
- Postmarketing cases of cutaneous vasculitis including
leukocytoclastic vasculitis, urticarial vasculitis, and IgA
vasculitis have been reported in patients receiving TAGRISSO.
Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate
for systemic involvement, and consider dermatology consultation. If
no other etiology can be identified, consider permanent
discontinuation of TAGRISSO based on severity
- Aplastic anemia has been reported in patients treated with
TAGRISSO in clinical trials (0.06% of 1813) and postmarketing. Some
cases had a fatal outcome. Inform patients of the signs and
symptoms of aplastic anemia including but not limited to, new or
persistent fevers, bruising, bleeding, and pallor. If aplastic
anemia is suspected, withhold TAGRISSO and obtain a hematology
consultation. If aplastic anemia is confirmed, permanently
discontinue TAGRISSO. Perform complete blood count with
differential before starting TAGRISSO, periodically throughout
treatment, and more frequently if indicated
- Verify pregnancy status of females of reproductive potential
prior to initiating TAGRISSO. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with TAGRISSO and
for 6 weeks after the final dose. Advise males with female partners
of reproductive potential to use effective contraception for 4
months after the final dose
- Because of the potential for serious adverse reactions in
breastfed infants from TAGRISSO, women should not breastfeed during
treatment with TAGRISSO and for 2 weeks after the final dose.
- Most common (≥20%) adverse reactions, including laboratory
abnormalities, were:
- TAGRISSO monotherapy: leukopenia, lymphopenia,
thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain,
neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
- TAGRISSO in combination with pemetrexed and platinum-based
chemotherapy: leukopenia, thrombocytopenia, neutropenia,
lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin,
and increased blood creatinine
INDICATIONS
- [TAGRISSO is indicated as adjuvant therapy after tumor
resection in adult patients with non-small cell lung cancer (NSCLC)
whose tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test]
- [TAGRISSO is indicated for the first-line treatment of adult
patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test]
- [TAGRISSO is indicated in combination with pemetrexed and
platinum-based chemotherapy, for the first-line treatment of adult
patients with locally advanced or metastatic NSCLC whose tumors
have epidermal growth factor receptor (EGFR) exon 19 deletions or
exon 21 L858R mutations, as detected by an FDA-approved test]
- [TAGRISSO is indicated for the treatment of adult patients with
metastatic epidermal growth factor receptor (EGFR) T790M
mutation-positive NSCLC, as detected by an FDA-approved test, whose
disease has progressed on or after EGFR tyrosine kinase inhibitor
(TKI) therapy]
Please see complete Prescription Information, including Patient
Information for TAGRISSO.
You may report side effects related to AstraZeneca products by
clicking here
Notes
Lung cancer
Lung cancer is the leading cause of cancer death among both men
and women, accounting for about one-fifth of all cancer deaths.7
Lung cancer is broadly split into NSCLC and small cell lung
cancer.2 The majority of all NSCLC patients are diagnosed with
advanced disease.4
Patients with EGFRm NSCLC are particularly sensitive to
treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which
blocks the cell-signaling pathways that drive the growth of tumor
cells.8
FLAURA2
FLAURA2 is a randomized, open-label, multi-center, global Phase
III trial in the 1st-line treatment of patients with locally
advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC.
Patients were treated with TAGRISSO 80mg once daily oral tablets
with the addition of chemotherapy (pemetrexed (500mg/m2) plus
cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for
four cycles, followed by TAGRISSO with pemetrexed maintenance every
three weeks.
The trial enrolled 557 patients in more than 150 centers across
more than 20 countries, including in the US, Europe, South America
and Asia. The primary endpoint is PFS. The trial is ongoing and
will continue to assess the secondary endpoint of OS.
TAGRISSO®
TAGRISSO® (osimertinib) is a third-generation, irreversible
EGFR-TKI with proven clinical activity in NSCLC, including against
CNS metastases. TAGRISSO (40mg and 80mg once-daily oral tablets)
has been used to treat more than 800,000 patients across its
indications worldwide and AstraZeneca continues to explore TAGRISSO
as a treatment for patients across multiple stages of EGFRm
NSCLC.
There is an extensive body of evidence supporting the use of
TAGRISSO in EGFRm NSCLC. TAGRISSO is the only targeted therapy to
improve patient outcomes in both early-stage disease in the ADAURA
Phase III trial and late-stage disease in the FLAURA Phase III
trial and FLAURA2 Phase III trial.
The Company is also researching ways to address tumor mechanisms
of resistance through the SAVANNAH and ORCHARD Phase II trials, and
the SAFFRON Phase III trial, which test TAGRISSO plus savolitinib,
an oral, potent and highly selective MET TKI, as well as other
potential new medicines.
AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer
to cure through the detection and treatment of early-stage disease,
while also pushing the boundaries of science to improve outcomes in
the resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung
cancer medicines and the next wave of innovations, including
TAGRISSO and IRESSA (gefitinib); IMFINZI (durvalumab) and IMJUDO
(tremelimumab-aclt); ENHERTU (fam-trastuzumab deruxtecan-nxki) and
datopotamab deruxtecan in collaboration with Daiichi Sankyo;
ORPATHYS (savolitinib) in collaboration with HUTCHMED; as well as a
pipeline of potential new medicines and combinations across diverse
mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance,
a global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer, including and
beyond treatment.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the
ambition to provide cures for cancer in every form, following the
science to understand cancer and all its complexities to discover,
develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyze changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines in Oncology, Rare Diseases and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. Please visit
www.astrazeneca-us.com and follow us on social media
@AstraZeneca.
References
- ASCO. Lung Cancer - Non-Small Cell: Introduction. Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment.
Accessed February 2024.
- LUNGevity Foundation. Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed February 2024.
- American Cancer Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html#:~:text=About%2080%25%20to%2085%25%20of,(outlook)%20are%20often%20similar.
Accessed February 2024.
- Cagle PT, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab Med.
2013;137:1191-1198.
- Keedy VL, et al. American Society of Clinical Oncology
Provisional Clinical Opinion: Epidermal Growth Factor Receptor
(EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell
Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor
Therapy. J Clin Oncol. 2011:29;2121-27.
- NCCN, National Comprehensive Cancer Network® (NCCN®).
Referenced with permission from the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung
Cancer Version 1.2024.© National Comprehensive Cancer Network, Inc.
[2024]. All rights reserved. Accessed [February 14, 2024]. To view
the most recent and complete version of the guideline, go online to
NCCN.org. NCCN makes no warranties of any kind whatsoever regarding
their content, use or application and disclaims any responsibility
for their application or use in any way.
- World Health Organisation. International Agency for Research on
Cancer. Lung Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed February 2024.
- Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes
T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer
Discov. 2014;4(9):1046-1061.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240216171764/en/
Media Inquiries Brendan McEvoy, +1 302 885 2677 Chelsea
Tressler, +1 302 885 2677 US Media Mailbox:
usmediateam@astrazeneca.com
AstraZeneca (NASDAQ:AZN)
過去 株価チャート
から 4 2024 まで 5 2024
AstraZeneca (NASDAQ:AZN)
過去 株価チャート
から 5 2023 まで 5 2024