59% of these patients treated with TAGRISSO
plus chemotherapy had complete brain tumor responses in FLAURA2
Phase III trial
Results from a prespecified exploratory analysis of the FLAURA2
Phase III trial showed AstraZeneca’s TAGRISSO® (osimertinib) with
the addition of chemotherapy demonstrated a 42% improvement in
central nervous system (CNS) progression-free survival (PFS),
compared to TAGRISSO alone for patients with locally advanced or
metastatic epidermal growth factor receptor-mutated (EGFRm)
non-small cell lung cancer (NSCLC) and brain metastases at
baseline, representing 40% of patients in the trial, as assessed by
blinded independent central review (BICR).
These results were presented today in an oral presentation at
the European Society for Medical Oncology (ESMO) Congress in
Madrid, Spain (abstract #LBA68).
In this group of patients, TAGRISSO with the addition of
chemotherapy reduced the risk of CNS disease progression or death
by 42% compared to TAGRISSO alone (based on a hazard ratio [HR] of
0.58; 95% confidence interval [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.
Results also showed a higher proportion of patients demonstrated
CNS complete response (CR) with TAGRISSO plus chemotherapy (59%)
versus TAGRISSO alone (43%).
David Planchard, MD, PhD, thoracic oncologist at Gustave Roussy
Institute of Oncology and principal investigator for the trial,
said: “Osimertinib has a proven ability to cross the blood-brain
barrier and improve outcomes for patients with lung cancer and
central nervous system metastases, who often face a poorer
prognosis than patients whose disease has not spread to the brain.
In FLAURA2, the addition of chemotherapy to osimertinib led to a
complete response and the disappearance of these tumors in the
brain, in more than half of these patients.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “In this trial, patients with brain metastases
at baseline saw a meaningful benefit with the FLAURA2 regimen,
offering hope for patients whose cancer has spread to the brain.
These data build on the recent positive progression-free survival
results from FLAURA2, further reinforcing TAGRISSO as the backbone
therapy in EGFR-mutated non-small cell lung cancer.”
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 (AEs) rates
were higher in the TAGRISSO plus chemotherapy arm, driven by
well-characterised chemotherapy-related AEs. TAGRISSO
discontinuation rates were low in both arms of the trial (11% for
the TAGRISSO plus chemotherapy arm and 6% for the monotherapy
arm).
In the TAGRISSO plus chemotherapy arm, patients remained on
TAGRISSO for a median duration of 22.3 months, while patients had a
median exposure to platinum-based chemotherapy of 2.8 months and a
median exposure to pemetrexed of 8.3 months.
Summary of results: FLAURA2 CNS efficacyi
TAGRISSO plus chemotherapy
(n=118)
TAGRISSO monotherapy
(n=104)
PFS HR (95% CI)
0.58 (0.33-1.01)
Median PFS (months; 95% CI)
30.2 (28.4-NCii)
27.6 (22.1-NC)
CNS objective response rate, n (%)
86 (73)
72 (69)
CR, n (%)
70 (59)
45 (43)
Median CNS duration of response (in
months; 95% CI)
NRiii (23.8-NC)
26.2 (19.4-NC)
i The data cut-off date was April 3,
2023.
ii NC, non-calculable
iii NR, not reached
Earlier this month, TAGRISSO with the addition of chemotherapy
was granted Priority Review by the Food and Drug Administration
(FDA) for the 1st-line treatment of adult patients with locally
advanced or metastatic EGFRm NSCLC based on positive PFS data from
the FLAURA2 Phase III trial recently presented at the International
Association for the Study of Lung Cancer 2023 World Conference on
Lung Cancer. In August 2023, TAGRISSO with the addition of
chemotherapy also received Breakthrough Therapy Designation from
the FDA in this setting.
IMPORTANT SAFETY INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% 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 Stevens-Johnson syndrome
(SJS) and erythema multiforme major (EMM) have been reported in
patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM 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 post marketing.
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 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.1
Lung cancer is broadly split into NSCLC and small cell lung
cancer.2 The majority of all NSCLC patients are diagnosed with
advanced disease.3
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 tumour
cells.4
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. 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 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.
There is an extensive body of evidence supporting the use of
TAGRISSO in EGFRm NSCLC. TAGRISSO is the only targeted therapy to
improve survival in both early-stage disease in the ADAURA Phase
III trial and late-stage disease in the FLAURA Phase III trial.
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), in the neoadjuvant
setting (NeoADAURA), 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
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
- 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 October 2023.
- LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed October 2023.
- Cancer.Net. Lung Cancer - Non-Small Cell: Statistics.
Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed October 2023.
- 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-81597 Last Updated 10/23
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231021219386/en/
Media Inquiries Brendan McEvoy, +1 302 885 2677 Chelsea
Ford , +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
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