23 December 2024
Tagrisso approved in the EU for
patients
with
unresectable EGFR-mutated
lung cancer
First and only EGFR inhibitor
and targeted treatment
approved
in the EU in unresectable NSCLC
Approval
based on LAURA Phase III trial results which showed
Tagrisso
extended
median progression-free survival to more than three
years
AstraZeneca's Tagrisso (osimertinib) has been
approved in the European Union (EU) for the treatment of adult
patients with locally advanced, unresectable non-small cell lung
cancer (NSCLC) whose tumours have epidermal growth factor receptor
(EGFR) exon 19 deletions
or exon 21 (L858R) substitution mutations and whose disease has not
progressed during or following platinum-based chemoradiation
therapy (CRT).
The approval by the European
Commission follows the
positive opinion of the
Committee for Medicinal Products for Human Use and is based on
results from the
LAURA Phase III trial, which
were 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 0.16; 95% confidence interval 0.10-0.24; p<0.001)
as assessed by blinded independent central review. Median
progression-free survival (PFS) was 39.1 months in patients treated
with Tagrisso
versus 5.6 months for placebo.
Overall survival (OS) results remain
immature, and the trial is continuing to assess OS as a secondary
endpoint.
Each year in Europe, there are more
than 450,000 people diagnosed with lung cancer, and approximately
80-85% have NSCLC.1-3 Among those with NSCLC in Europe,
about 10-15% have tumours with an EGFR
mutation.4-6
Manuel Cobo, MD, Specialist Physician
of the Medical Oncology Service at the Carlos Haya University
Hospital, Malaga, Spain, and investigator for the trial, said:
"Today's approval marks a major breakthrough for patients in the EU
with unresectable, EGFR-mutated non-small cell lung
cancer, delivering the first targeted treatment in this setting.
Osimertinib reduced the risk of disease progression or death by an
unprecedented 84 per cent in the LAURA trial, setting a new
benchmark for outcomes and underscoring the importance of testing
for EGFR mutations upon
diagnosis."
Dave Fredrickson,
Executive Vice President, Oncology Business Unit, AstraZeneca,
said: "Tagrisso is now the first and
only EGFR inhibitor
and targeted treatment approved in the EU for locally
advanced, unresectable lung cancer, providing a new standard of
care to patients who have historically experienced early
progression after chemoradiation
therapy. The powerful results from the
LAURA trial show Tagrisso
improves outcomes for patients in the unresectable setting,
reinforces the importance of timely EGFR testing and solidifies
Tagrisso as the backbone
therapy in EGFR-mutated
non-small cell lung cancer."
The safety and tolerability of
Tagrisso in the LAURA
trial was consistent with its established profile and no new safety
concerns were identified.
This is the fifth major approval
for Tagrisso based on the LAURA
trial following recent approvals in the US,
Switzerland, South Korea and Australia. Regulatory applications are
also currently under review in China, Japan and several other
countries.
Tagrisso is approved as
monotherapy in more than 100 countries including in the US, EU,
China and Japan. Approved indications include 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 is also approved in
combination with chemotherapy in the US, China and several other
countries for 1st-line treatment of patients with locally advanced
or metastatic EGFRm
NSCLC.
Notes
Lung cancer
Each year, an estimated 2.4 million
people are diagnosed with lung cancer globally.7 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, with 80-85% of patients diagnosed with
NSCLC, the most common form of lung cancer.2,3 The
majority of all NSCLC patients are diagnosed with advanced
disease.8
Approximately 10-15% of NSCLC
patients in the US and Europe, and 30-40% of patients in Asia have
EGFRm NSCLC.4-6
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.9
LAURA
LAURA is a randomised, double-blind,
placebo-controlled, multi-centre, 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 80mg once-daily
oral tablets until disease progression, unacceptable toxicity or
other discontinuation criteria were met. Upon progression, patients
in the placebo arm were offered
treatment with Tagrisso.
The trial enrolled 216 patients in
more than 145 centres across more than 15 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 metastases.
Tagrisso (40mg and 80mg
once-daily oral tablets) has been used to treat 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 as standard of care in
EGFRm NSCLC. Tagrisso improved patient outcomes in
early-stage disease in the
ADAURA Phase III trial,
Stage III, unresectable disease in the LAURA
Phase III trial,
late-stage disease in the
FLAURA Phase III trial, and with
chemotherapy in the
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 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 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's innovative
medicines are sold in more than 125 countries and 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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Cancer incidence and mortality patterns in Europe: Estimates for 40
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https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html.
Accessed December 2024.
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Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed December 2024.
4. 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
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2011;29:2121-2127.
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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.
7. World Health
Organization. International Agency for Research on Cancer. Lung
Cancer Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed December 2024.
8. González M, et al.
Overall survival for early and locally advanced non-small-cell lung
cancer from one institution: 2000-2017. Clin Transl Oncol.
2021;23(7):1325-1333.
9. Cross DA, et al.
AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated
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2014;4(9):1046-1061.
Adrian Kemp
Company Secretary
AstraZeneca PLC