Combination reduced the risk of disease
progression by 38% versus TAGRISSO monotherapy, the current
1st-line global standard of care
Positive results from the FLAURA2 Phase III trial showed
AstraZeneca’s TAGRISSO® (osimertinib) in combination with
chemotherapy demonstrated a statistically significant and
clinically meaningful improvement in progression-free survival
(PFS), compared to TAGRISSO alone for patients with locally
advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal
growth factor receptor-mutated (EGFRm) non-small cell lung cancer
(NSCLC).
These results were presented today in a Presidential Symposium
at the International Association for the Study of Lung Cancer
(IASLC) 2023 World Conference on Lung Cancer (WCLC) (abstract
#PL03).
Results showed TAGRISSO plus chemotherapy reduced the risk of
disease progression or death by 38% compared to TAGRISSO alone
(based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI]
0.49-0.79; p<0.0001). By investigator assessment, the
combination extended median PFS by 8.8 months versus TAGRISSO
alone. PFS results from blinded independent central review (BICR)
were consistent, showing TAGRISSO plus chemotherapy extended median
PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80;
p=0.0002). Importantly, a clinically meaningful PFS benefit was
observed across all prespecified subgroups, including sex, race,
type of EGFR mutation, age at time of diagnosis, smoking history
and central nervous system (CNS) metastasis status at baseline.
At the time of this analysis, the overall survival (OS) data
were immature however, a favorable trend was observed for TAGRISSO
plus chemotherapy.
Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer
Institute and principal investigator for the FLAURA2 trial, said:
“Patients received nearly nine additional months before their
EGFR-mutated non-small cell lung cancer progressed as a result of
the addition of chemotherapy to standard-of-care osimertinib,
building on the strong efficacy we have already seen with
osimertinib monotherapy. With these convincing data, patients may
soon have a choice of two highly effective osimertinib-based
treatment options in this advanced disease setting.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The compelling FLAURA2 results add to the
extensive evidence supporting TAGRISSO as the backbone therapy in
EGFR-mutated non-small cell lung cancer and establish a new
benchmark for progression-free survival in this setting. We look
forward to bringing this potential treatment regimen to patients
with advanced lung cancer to further delay disease progression,
especially for patients with the greatest unmet need including
those with central nervous system metastasis at diagnosis.”
Summary of results: FLAURA2
PFS by INV
PFS by BICR
TAGRISSO plus chemotherapy
(n=279)
TAGRISSO monotherapy
(n=278)
TAGRISSO plus chemotherapy
(n=279)
TAGRISSO monotherapy
(n=278)
Median PFS (in months)i
25.5
(24.7, NCii)
16.7
(14.1, 21.3)
29.4
(25.1, NCii)
19.9
(16.6, 25.3)
Hazard ratio (95% CI)
0.62 (0.49-0.79)
0.62 (0.48-0.80)
p-value
<0.0001
0.0002
Data maturity
51%
43%
i. Data cut-off date was 3 April 2023.
ii. NC: Not calculable
Safety results and discontinuation rates due to adverse events
(AEs) were consistent with the established profiles of each
medicine and no new safety concerns were reported. Grade 3 or
higher AEs from all causes occurred in 64% of patients in the
TAGRISSO plus chemotherapy arm versus 27% in the TAGRISSO
monotherapy arm.
IMPORTANT SAFETY
INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.8% of
the 1479 TAGRISSO-treated patients; 0.3% 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 is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurs in
TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in
clinical trials, 0.8% were found to have a QTc >500 msec, and
3.1% 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% of the 1479 TAGRISSO-treated
patients; 0.1% of cardiomyopathy cases were fatal. A decline in
left ventricular ejection fraction (LVEF) ≥10% from baseline and to
<50% LVEF occurred in 3.2% of 1233 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%. Conduct cardiac
monitoring, including assessment of LVEF at baseline and during
treatment, in patients with cardiac risk factors. 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 0.7% of 1479 patients treated with
TAGRISSO 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 (0.07% of 1479) 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
- Most common (≥20%) adverse reactions, including laboratory
abnormalities, were leukopenia, lymphopenia, thrombocytopenia,
diarrhea, anemia, rash, musculoskeletal pain, nail toxicity,
neutropenia, dry skin, stomatitis, fatigue, and cough
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 for the treatment of adult patients with
metastatic 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 Prescribing 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.1
Lung cancer is broadly split into NSCLC and small cell lung
cancer.2 Each year, there are an estimated 2.2 million people
diagnosed with lung cancer globally with 80-85% of patients
diagnosed with NSCLC, the most common form of lung cancer.1-3
Approximately 70% of people are diagnosed with advanced NSCLC.4
Approximately 10-15% of NSCLC patients in the US and Europe, and
30-40% of patients in Asia have EGFRm NSCLC.5-7 Patients with EGFRm
NSCLC are particularly sensitive to treatment with an EGFR-tyrosine
kinase inhibitor (EGFR-TKI) which blocks the cell-signalling
pathways that drive the growth of tumour 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 in
combination with 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. 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®
TAGRISSO® (osimertinib) is a third-generation, irreversible
EGFR-TKI with proven clinical activity in NSCLC, including against
central nervous system (CNS) metastasis. TAGRISSO (40mg and 80mg
once-daily oral tablets) has been used to treat nearly 700,000
patients across its indications worldwide and AstraZeneca continues
to explore TAGRISSO as a treatment for patients across multiple
stages of EGFRm NSCLC.
TAGRISSO, the only targeted therapy to improve survival in both
early- and late-stages of EGFRm NSCLC, is approved as monotherapy
in more than 100 countries including in the US, EU, China and
Japan. These include for 1st-line treatment of patients with
locally advanced or metastatic EGFRm NSCLC (FLAURA), locally
advanced or metastatic EGFR T790M mutation-positive NSCLC, and
adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC
(ADAURA), where TAGRISSO recently demonstrated a statistically
significant and clinically meaningful OS benefit.
AstraZeneca also has several ongoing Phase III trials focused on
earlier stages of lung cancer including a trial in the Stage
IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III
locally advanced unresectable setting (LAURA).
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
tremelimumab-actl 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.
AstraZeneca (LSE/STO/Nasdaq: AZN) 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 astrazeneca-us.com and follow the
Company on Social Media @AstraZeneca.
References
- 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 August 2023.
- LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed August 2023.
- Cheema PK, et al. Perspectives on treatment advances for stage
III locally advanced unresectable non-small-cell lung cancer. Curr
Oncol. 2019;26(1):37-42.
- Cancer.Net. Lung Cancer - Non-Small Cell: Statistics. Available
at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed August 2023.
- Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on
Cytological and Histological Samples in Non-Small Cell Lung Cancer:
a Polish, Single Institution Study and Systematic Review of
European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
- 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.
- Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a
Review of Available Methods and Their Use for Analysis of Tumour
Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
- 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-80077 Last Updated 09/23
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Media Inquiries Brendan McEvoy +1 302 885 2677 Jillian
Gonzales +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
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