Decision based on LAURA Phase III trial
results which extended median progression-free survival by more
than three years
TAGRISSO also granted Breakthrough Therapy
Designation in US in this setting
AstraZeneca’s supplemental New Drug Application (sNDA) for
TAGRISSO® (osimertinib) has been accepted and granted Priority
Review in the US for the treatment of adult patients with
unresectable, Stage III epidermal growth factor receptor-mutated
(EGFRm) non-small cell lung cancer (NSCLC) after chemoradiotherapy
(CRT). If approved, TAGRISSO will be indicated for EGFRm patients
whose tumors have exon 19 deletions or exon 21 (L858R)
mutations.
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that, if approved, would offer
significant improvements over available options by demonstrating
safety or efficacy improvements, preventing serious conditions or
enhancing patient compliance.1 The Prescription Drug User Fee Act
date, the FDA action date for their regulatory decision, is
anticipated during the fourth quarter of 2024.
TAGRISSO was also recently granted Breakthrough Therapy
Designation (BTD) by the FDA in this setting. BTD accelerates the
development and regulatory review of potential new medicines
intended to treat a serious condition and address a significant
unmet medical need.2
Each year in the US, there are nearly 200,000 people diagnosed
with lung cancer, and 80-85% of these patients are diagnosed with
NSCLC, the most common form of lung cancer.3-5 Approximately 15% of
NSCLC patients in the US have EGFR mutations.6 Nearly one in five
newly diagnosed individuals with NSCLC are unresectable.7
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “Priority Review of TAGRISSO in this early-stage
curative setting is important for patients who currently have no
targeted treatments available. We look forward to close
collaboration with the FDA on an accelerated path to bring TAGRISSO
to patients as a potential new standard of care as quickly as
possible. TAGRISSO continues to serve patients as a backbone
therapy in EGFR-mutated lung cancer, extending progression-free
survival in the LAURA trial by more than three years and
reinforcing the importance of testing for EGFR mutations at the
time of diagnosis.”
The sNDA is based on data from the LAURA Phase III trial
recently presented during the Plenary Session at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting and
simultaneously published in The New England Journal of
Medicine.
In the trial, TAGRISSO reduced the risk of disease progression
or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95%
confidence interval [CI] 0.10-0.24; p<0.001) as assessed by
blinded independent central review (BICR). Median progression-free
survival (PFS) was 39.1 months in patients treated with TAGRISSO
versus 5.6 months for placebo. Importantly, a clinically meaningful
PFS benefit was observed across all prespecified subgroups
including sex, race, type of EGFR mutation, age, smoking history,
and prior CRT.
Overall survival (OS) data showed a favorable trend for
TAGRISSO, although data were not mature at the time of this
analysis. The trial will continue to assess OS as a secondary
endpoint.
Safety results and discontinuation rates due to adverse events
were consistent with its known profile and no new safety concerns
were identified.
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. TAGRISSO with the addition of chemotherapy is also
approved in the US and several other countries for 1st-line
treatment of patients with locally advanced or metastatic EGFRm
NSCLC.
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.8
Lung cancer is broadly split into NSCLC and small cell lung
cancer.4 The majority of all NSCLC patients are diagnosed with
advanced disease.9
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.10
LAURA
LAURA is a randomized, double-blind, placebo-controlled,
multi-center, global Phase III trial in patients with unresectable,
Stage III EGFRm NSCLC whose disease has not progressed following
definitive platinum‑based CRT. Patients were treated with TAGRISSO
80 mg once daily oral tablets until disease progression,
unacceptable toxicity or other discontinuation criteria were met.
Upon progression, patients in the placebo arm were permitted to be
treated with TAGRISSO.
The trial enrolled 216 patients in more than 145 centers across
more than 15 countries, including in the US, Europe, South America
and Asia. This is the analysis of the primary endpoint of PFS. The
trial is ongoing and will continue to assess the secondary endpoint
of OS.
TAGRISSO® (osimertinib)
TAGRISSO® (osimertinib) is a third-generation, irreversible
EGFR-TKI with proven clinical activity in NSCLC, including against
central nervous system (CNS) metastases. TAGRISSO (40 mg and 80 mg
once-daily oral tablets) has been used to treat nearly 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 early-stage disease in the ADAURA Phase
III trial, locally advanced stages in the LAURA Phase III trial and
late-stage disease in the FLAURA Phase III trial and FLAURA2 Phase
III trial.
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.
The Company is also researching ways to address tumors
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 gefitinib; durvalumab and tremelimumab-actl;
fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in
collaboration with Daiichi Sankyo; 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
- FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed June 2024.
- FDA. Frequently Asked Questions: Breakthrough Therapies.
Available at:
https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies.
Accessed June 2024.
- National Cancer Institute. Cancer Stat Facts: Lung and Bronchus
Cancer. Available at:
https://seer.cancer.gov/statfacts/html/lungb.html. Accessed June
2024.
- LUNGevity Foundation. Types of Lung Cancer. Available at:
https://www.lungevity.org/lung-cancer-basics/types-of-lung-cancer.
Accessed June 2024.
- American Cancer Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html.
Accessed June 2024.
- 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.
- Quint LE. Lung cancer: assessing resectability. Cancer Imaging.
2003;4(1):15-8.
- World Health Organisation. International Agency for Research on
Cancer. Lung Fact Sheet. Available at
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed June 2024.
- Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab Med.
2013;137:1191-1198.
- 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.
US-90388 Last Updated 06/24
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