19 February 2024
Tagrisso
demonstrated
overwhelming efficacy benefit for patients with unresectable, Stage
III EGFR-mutated lung cancer in LAURA Phase III
trial
First EGFR inhibitor and targeted treatment to
demonstrate
progression-free survival benefit in Stage
III setting
Positive high-level results from the LAURA
Phase III trial showed AstraZeneca's Tagrisso (osimertinib) demonstrated a
statistically significant and highly clinically meaningful
improvement in progression-free survival (PFS) for patients with
unresectable, Stage III epidermal growth
factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC)
after chemoradiotherapy (CRT) compared to placebo
after CRT.
Overall survival (OS) data showed a favourable trend
for Tagrisso, although
data were not mature at the time of this analysis. The trial will
continue to assess OS as a secondary endpoint.
Each year an estimated 2.4 million people are
diagnosed with lung cancer globally with 80-85% of patients
diagnosed with NSCLC, the most common form of lung
cancer.1-3 Approximately 10-15% of
NSCLC patients in the US and Europe, and 30-40% of patients in
Asia, have EGFR mutations.4-7 More than one in six patients with NSCLC are
diagnosed with unresectable Stage III disease
(15%).8
Suresh Ramalingam, MD, Executive Director of Winship
Cancer Institute of Emory University, Atlanta, US, and principal
investigator in the trial, said: "These results represent a
major advance for patients with Stage III EGFR-mutated lung cancer
who have a high propensity for early progression and spread to the
brain, and where no targeted therapy is available. LAURA shows
osimertinib can provide impactful clinical benefit and could become
the first targeted treatment option for patients with Stage III
disease."
Susan Galbraith, Executive Vice President, Oncology
R&D, AstraZeneca, said: "These highly impactful results for the
LAURA trial in this potentially curative early lung cancer setting
further entrench Tagrisso
as the backbone therapy for EGFR-mutated lung cancer. These data
together with the ADAURA data, reinforce the imperative to diagnose
and treat patients with lung cancer as early as possible."
The safety and tolerability of Tagrisso in the LAURA trial was
consistent with its established profile and no new safety concerns
were reported with Tagrisso maintenance treatment
following CRT.
The data will be presented at a
forthcoming medical meeting and shared with global regulatory
authorities.
In addition, Tagrisso plus chemotherapy was
recently approved in the US based on 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 with results expected
later this year, and in the early-stage adjuvant resectable setting
in the ADAURA2 Phase III trial.
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.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.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 permitted to be treated 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. 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
metastases. Tagrisso (40mg
and 80mg once-daily oral tablets) has been used to treat more than
800,000 patients across its indications worldwide and AstraZeneca
continues to explore Tagrisso as a treatment for patients
across multiple stages of EGFRm NSCLC.
Tagrisso 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, locally advanced
or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant
treatment of early-stage (IB, II and IIIA) EGFRm NSCLC, where
Tagrisso recently
demonstrated a statistically significant and clinically meaningful
OS benefit.
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 both early-stage disease in
the
ADAURA Phase III trial and
late-stage disease in the
FLAURA Phase III trial and
FLAURA2 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
1. World Health
Organisation. International Agency for Research on Cancer. Lung
Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed February 2024.
2. LUNGevity Foundation.
Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed February 2024.
3. American Cancer
Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html#:~:text=About%2080%25%20to%2085%25%20of,(outlook)%20are%20often%20similar.
Accessed February 2024.
4. Knight SB, et al.
Progress and prospects of early detection in lung cancer. Open
Biol. 2017;7(9): 170070.
5. Keedy VL, et al.
American Society of Clinical Oncology Provisional Clinical Opinion:
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Patients with Advanced Non-Small-Cell Lung Cancer Considering
First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol.
2011:29;2121-27.
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prevalence of EGFR mutation in patients with non-small cell lung
cancer: a systematic review and meta-analysis. Oncotarget.
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A, et al. EGFR Mutation Testing on Cytological and Histological
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J Clin Exp Pathol. 2013:6;2800-12.
8. Cerner CancerMPact
database.Accessed October 2023.
9. 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.
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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