26 September 2024
Tagrisso approved in the US
for patients with
unresectable, Stage III EGFR-mutated lung cancer
Based on
LAURA Phase III trial results which showed Tagrisso
extended
median progression-free survival by more than three
years
AstraZeneca's Tagrisso (osimertinib)
has been approved in the US for the treatment of
adult patients with unresectable, Stage III
epidermal growth factor receptor-mutated (EGFRm) non-small cell
lung cancer (NSCLC) whose disease has not progressed during or
following concurrent or sequential platinum-based chemoradiation
therapy (CRT). Tagrisso is
indicated for patients with exon 19
deletions or exon 21 (L858R) mutations, as detected by a
FDA-approved test.
The approval follows a
Priority Review by the Food and
Drug Administration (FDA) that was based on results from the
LAURA Phase III trial,
which were presented during the Plenary Session at
the 2024 American Society of Clinical Oncology (ASCO) Annual
Meeting and simultaneously published in
The New England Journal of
Medicine.
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 at this current analysis. The trial continues to assess OS
as a secondary endpoint.
Each year in the US, there are more
than 200,000 people diagnosed with lung cancer, and 80-85% of these
patients are diagnosed with NSCLC, the most common form of lung
cancer.1-3 Approximately 15% of NSCLC patients in the US
have EGFR mutations.4 Nearly one in five people
diagnosed with NSCLC has an unresectable
tumour.5
Suresh Ramalingam, MD, Executive
Director of Winship Cancer Institute of Emory University, Atlanta,
US, and principal investigator in the trial, said: "This approval
represents a major breakthrough for patients with Stage III,
EGFR-mutated lung cancer who will now have the opportunity to
benefit from osimertinib. Patients treated with osimertinib lived
without disease progression by more than three years in the LAURA
trial, and this impressive benefit underscores the importance of
diagnosing and testing lung cancer patients as early as
possible."
Dave Fredrickson, Executive Vice
President, Oncology Business Unit, AstraZeneca, said: "The approval
of Tagrisso for
patients with Stage III, unresectable EGFR-mutated non-small cell
lung cancer addresses a critical need for patients with these
mutations who have never had the option of targeted therapy before.
The results of the LAURA trial show the powerful impact
Tagrisso can make as
backbone therapy in this disease, and with this approval, patients
across all stages of EGFR-mutated non-small cell lung cancer can
now benefit."
The safety and tolerability of
Tagrisso in the LAURA
trial was consistent with its established profile and no new safety
concerns were identified.
Tagrisso is approved for patients with EGFR mutations in the
1st-line metastatic setting as a monotherapy and in combination
with chemotherapy, and as an adjuvant treatment for early-stage
disease. Tagrisso is
currently under review with regulatory authorities in other
countries around the world for this indication.
Notes
Lung cancer
Each year, an estimated 2.4 million
people are diagnosed with lung cancer globally.6 Lung
cancer is the leading cause of cancer death among both men and
women, accounting for about one-fifth of all cancer
deaths.6 Lung cancer is broadly split into NSCLC and
small cell lung cancer.2 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.4,8-9 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. 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 (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 as standard of care in EGFRm
NSCLC. Tagrisso improved
patient outcomes in early-stage disease in the
ADAURA Phase III trial,
locally advanced 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 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 Orpathys (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;
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. Centers for Disease
Control and Prevention. U.S. Cancer Statistics Lung Cancer Stat
Bite. Available at:
https://www.cdc.gov/united-states-cancer-statistics/publications/lung-cancer-stat-bite.html.
Accessed August 2024.
2. LUNGevity Foundation.
Types of Lung Cancer. Available at:
https://www.lungevity.org/lung-cancer-basics/types-of-lung-cancer.
Accessed August 2024.
3. American Cancer
Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html.
Accessed August 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(15):2121-2127.
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2004;4(1):15-18.
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Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed August 2024.
7. Cagle P, et al. Lung
Cancer Biomarkers: Present Status and Future Developments.
Arch Pathol Lab Med.
2013;137(9):1191-1198.
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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2800-2812.
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.
2013;66(2):79-89.
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
