18 November 2024
Tagrisso
recommended for
approval in the EU by CHMP
for patients with
unresectable EGFR-mutated
lung cancer
Recommendation 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
recommended for approval 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 Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) based its
positive opinion on the results from the
LAURA Phase III trial, which were published
in The New England Journal of
Medicine.
Results showed 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.
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 at this current analysis. The trial continues to assess OS
as a 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, nearly one in five people with NSCLC
has an unresectable tumour.4
Manuel Cobo, MD, Specialist Physician of the
Medical Oncology Service at the Carlos Haya University Hospital,
Malaga, Spain, and investigator for the trial, said: "The LAURA
results build on the established efficacy of osimertinib and
support the approval of the first targeted therapy for patients
with unresectable, EGFR-mutated lung cancer. Today's
positive recommendation marks an important step towards offering
patients in Europe a targeted treatment option that can extend the
time before their disease progresses by more than three
years."
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Today's news reinforces
Tagrisso as the backbone
therapy in EGFR-mutated
non-small cell lung cancer, meeting the critical unmet need for an
effective targeted treatment option in the unresectable setting.
Tagrisso has now
demonstrated its benefit across all stages of EGFR-mutated lung cancer, representing
a pivotal step in transforming care for patients who are urgently
in need of innovative therapies that can help extend their
lives."
The safety and tolerability of Tagrisso in the LAURA trial was
consistent with its established profile and no new safety concerns
were identified.
Tagrisso following
CRT was recently approved for the treatment of adult patients with
unresectable, Stage III EGFRm NSCLC in the US.
Regulatory applications are also currently under review in
China, Japan and several other countries based on the LAURA
trial.
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.5 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 The
majority of all NSCLC patients are diagnosed with advanced
disease.6
Approximately 10-15% of NSCLC
patients in the US and Europe, and 30-40% of patients in Asia have
EGFRm NSCLC.7-9
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.10
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 (CNS)
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
1. Ferlay J, et al. Cancer incidence and mortality patterns in
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://www.lungevity.org/lung-cancer-basics/types-of-lung-cancer.
Accessed November 2024.
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Accessed November 2024.
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Future Developments. Arch Pathol
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7. 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(15):2121-2127.
8. 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
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9. 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.
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10. Cross DAE, 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