3 June 2024
Tagrisso
with the addition
of chemotherapy recommended for approval in
the EU by CHMP for patients
with EGFR-mutated advanced lung cancer
Recommendation 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 pemetrexed and platinum-based chemotherapy has been
recommended for approval in the European Union (EU) for 1st-line
treatment of adult patients with locally advanced or metastatic
epidermal growth factor receptor-mutated (EGFRm) non-small cell
lung cancer (NSCLC) whose tumours have exon 19
deletions or exon 21 (L858R) mutations.
The Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) based its
positive opinion on the results from the
FLAURA2 Phase III trial, which were also published
in The New
England Journal of Medicine.
Results showed 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).
While overall survival (OS) remained
immature at the second interim analysis (41% maturity), an
encouraging trend towards an OS benefit was observed with
Tagrisso plus chemotherapy
versus Tagrisso alone (HR
0.75; 95% CI 0.57-0.97). The trial continues to assess OS as a key
secondary endpoint.
Each year in Europe, there are more than
450,000 people diagnosed with lung cancer.1 Among those
with NSCLC, the most common form of lung cancer, about 10-15% of
patients in Europe have tumours with an EGFR
mutation.2,3 Additionally, the majority
of patients with NSCLC are diagnosed with advanced
disease.4
David Planchard, MD, PhD, thoracic oncologist
at Gustave Roussy Institute of Oncology and principal investigator
for the trial, said: "The FLAURA2 results build on the established
efficacy of osimertinib monotherapy in patients with EGFR-mutated
lung cancer, demonstrating a meaningful nine-month improvement in
progression-free survival with the addition of chemotherapy.
Today's positive recommendation is a vital step towards providing
patients in Europe with an additional treatment option capable of
extending the time before their disease progresses. This expands on
the already approved use of osimertinib as monotherapy, providing
physicians with options to tailor treatments that best suit their
patients' specific disease needs."
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Today's news reinforces the
importance of Tagrisso as
the backbone therapy in EGFR-mutated lung cancer. If approved in
Europe, patients will have the option to be treated with
Tagrisso alone, or with
chemotherapy, which is especially important when caring for
patients whose disease has spread to the brain or those with L858R
mutations."
The safety profile of Tagrisso plus 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-characterised chemotherapy-related AEs.
Discontinuation rates of Tagrisso due to AEs were 11%
for Tagrisso plus chemotherapy and 6%
for monotherapy.
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 the 1st-line treatment of patients with locally
advanced or metastatic EGFRm NSCLC.
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.5 Lung cancer is broadly
split into NSCLC and small cell lung cancer.3 Each year
there are an estimated 2.4 million people diagnosed with lung
cancer globally, with 80-85% of patients diagnosed with NSCLC, the
most common form of lung cancer.3,5-6 The majority of
all NSCLC patients are diagnosed with advanced
disease.7
Approximately 10-15% of NSCLC
patients in the US and Europe, and 30-40% of patients in Asia have
EGFRm NSCLC.8-10 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.11
FLAURA2
FLAURA2 is a randomised, open-label,
multi-centre, 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 centres 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 central nervous system (CNS)
metastases. Tagrisso (40mg
and 80mg 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 tumour 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); Enhertu (trastuzumab deruxtecan) 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 catalyse 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
AstraZeneca (LSE/STO/Nasdaq: AZN) is
a global, science-led biopharmaceutical company that focuses on the
discovery, development, and commercialisation 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.com
and follow the Company on social media
@AstraZeneca.
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References
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Europe: Estimates for 40 countries and 25 major cancers in 2018.
Eur J Cancer.
2018;103:356-387.
2. Sanden SV, et al. Prevalence of Epidermal Growth Factor
Receptor Exon 20 Insertion Mutations in Non-small-Cell Lung Cancer
in Europe: A Pragmatic Literature Review and Meta-analysis.
Targeted Onc.
2022;17:153-166.
3. LUNGevity Foundation. Types of Lung Cancer. Available at:
https://lungevity.org/for-
patientscaregivers/lung-cancer-101/types-of-lung-cancer.
Accessed May 2024.
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Lung Cancer Biomarkers: Present Status and Future Developments.
Archives Pathology Lab
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Accessed May 2024.
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Accessed May 2024.
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Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed May 2024.
8. 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.
9. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples
in Non-Small Cell Lung Cancer: a Polish, Single Institution
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10. 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.
11. 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.
Adrian
Kemp
Company Secretary
AstraZeneca
PLC