Tagrisso demonstrated superior
progression-free survival (PFS) of 18.9 months compared with 10.2
months for the current standard of care and an encouraging
preliminary overall survival benefit
AstraZeneca today announced that the New England Journal of
Medicine has published the positive results from the Phase III
FLAURA trial which provide data for Tagrisso’s (osimertinib) use in
the 1st-line treatment of adult patients with locally advanced or
metastatic epidermal growth factor receptor (EGFR)-mutated
non-small cell lung cancer (NSCLC).1 The trial showed a
statistically significant, clinically meaningful progression-free
survival (PFS) advantage for osimertinib, a third-generation,
irreversible EGFR tyrosine kinase inhibitor (TKI), compared with
current 1st-line EGFR-TKIs, erlotinib or gefitinib.1
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Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA
trial, from the Winship Cancer Institute of Emory University,
Atlanta, USA, said: “The results of the FLAURA trial may herald a
shift in how we treat patients with EGFR-mutated NSCLC. The data
demonstrate superiority of osimertinib compared to current standard
EGFR-TKIs in the 1st-line setting.”
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said:
“EGFR-mutated NSCLC patients need new therapies that improve
outcomes. The data published in NEJM today further emphasise the
potential of osimertinib as a new treatment standard in this
patient population.”
In the Phase III FLAURA trial, osimertinib significantly
improved PFS compared to erlotinib or gefitinib in previously
untreated patients with locally advanced or metastatic EGFR-mutated
(EGFRm) NSCLC. Median PFS was nearly doubled at 18.9 months for
osimertinib compared with 10.2 months for the EGFR-TKI comparator
arm (PFS, hazard ratio [HR] 0.46; 95% confidence interval [CI]
0.37-0.57; p<0.001). Preliminary overall survival (OS) data
favoured osimertinib with a 37% reduction in the risk of death (HR
0.63, 95% CI 0.45-0.88; p=0.007 [not significant]) at the interim
OS analysis (25% maturity).1
The FLAURA safety data for osimertinib were in line with those
observed in prior clinical trials. Osimertinib was well tolerated,
with less frequent grade 3 or higher adverse events (AEs) than with
standard EGFR-TKIs (34% vs. 45%). In all patients, the most common
AEs were rash or acne (58% [1% Grade ≥3] for osimertinib vs. 78%
[7% Grade ≥3] for the comparator arm), diarrhoea (58% [2% Grade ≥3]
for osimertinib vs. 57% [2% Grade ≥3] for the comparator arm), and
dry skin (36% [<1% Grade ≥3] for osimertinib vs. 36% [1% Grade
≥3] for the comparator arm).1
AstraZeneca presented the full FLAURA data at the Presidential
Symposium of the European Society of Medical Oncology (ESMO) 2017
Congress in Madrid, Spain, in September.
NOTES TO EDITORS
About NSCLCLung cancer is the leading cause of cancer
death among both men and women, accounting for about one-quarter of
all cancer deaths, more than breast, prostate and colorectal
cancers combined.2 Approximately 10-15% of patients in the US and
Europe, and 30-40% of patients in Asia have EGFRm NSCLC.3,4,5 These
patients are particularly sensitive to treatment with currently
available EGFR-TKIs, which block the cell-signaling pathways that
drive the growth of tumour cells.6 However, tumours almost always
develop resistance to EGFR-TKI treatment leading to disease
progression.7 Approximately half of patients develop resistance to
approved EGFR-TKIs such as gefitinib and erlotinib due to the
resistance mutation, EGFR T790M. Osimertinib also targets this
secondary mutation that leads to disease progression.7,8 There is
also a need for medicines with improved CNS efficacy, since
approximately 25% of patients with EGFR-mutated NSCLC have brain
metastases at diagnosis, increasing to approximately 40% within two
years of diagnosis.9
About TagrissoTagrisso (osimertinib) is a
third-generation, irreversible EGFR-TKI designed to inhibit both
EGFR-sensitising and EGFR T790M-resistance mutations, with clinical
activity against CNS metastases.10 Osimertinib 40mg and 80mg
once-daily oral tablets have been approved in more than 60
countries, including the US, EU, Japan and China, for patients with
EGFR T790M mutation-positive advanced NSCLC. Osimertinib is also
being investigated in the adjuvant setting and in combination with
other treatments.11,12
About FLAURAThe FLAURA trial assessed the efficacy and
safety of osimertinib 80mg once daily vs. standard-of-care
EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib
[250mg orally, once daily]) in previously untreated patients with
locally advanced or metastatic EGFR-mutated NSCLC.13 The trial was
a double-blinded, randomised study, with 556 patients across 29
countries.13
About AstraZeneca in Lung CancerAstraZeneca is committed
to developing medicines to help every patient with lung cancer. We
have two approved medicines and a growing pipeline that targets
genetic changes in tumour cells and boosts the power of the immune
response against cancer. Our unrelenting pursuit of science aims to
deliver more breakthrough therapies with the goal of extending and
improving the lives of patients across all stages of disease and
lines of therapy.
About AstraZeneca in OncologyAstraZeneca has a
deep-rooted heritage in Oncology and offers a quickly-growing
portfolio of new medicines that has the potential to transform
patients’ lives and the Company’s future. With at least six new
medicines to be launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development, we are
committed to advance New Oncology as one of AstraZeneca’s five
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our investment in
Acerta Pharma in haematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates – and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and one day eliminate cancer as a cause
of death.
About AstraZenecaAstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular & Metabolic Diseases and Respiratory.
The Company also is selectively active in the areas of
autoimmunity, neuroscience, and infection. AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide.
For more information, please
visit www.astrazeneca.com and follow us on Twitter
@AstraZeneca.
Intended audiencesThis press release is issued from
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References
1 Soria, JC, et al. Osimertinib in EGFR Mutation-Positive
Advanced Non-Small Cell Lung Cancer. NEJM. To be published 18 Nov
2017.
2 American Cancer Society. Key Statistics for Lung Cancer.
Available at
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html.
Accessed November 2017.
3 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 Systematic Review of
European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
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 First-Line EGFR Tyrosine Kinase Inhibitor
Therapy. J Clin Oncol. 2011:29;2121-27.
5 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.
6 Langer CJ, et al. Epidermal Growth Factor Receptor Inhibition
in Mutation-Positive Non-Small-Cell Lung Cancer: Is Afatinib Better
or Simply Newer? J Clin Oncol. 2013:31(27);3303-05.
7 Yu HA, et al. Analysis of Tumour Specimens at the Time of
Acquired Resistance to EGFR-TKI Therapy in 155 Patients with
EGFR-Mutant Lung Cancer. Clin Cancer Research.
2013:19(8);2240-46.
8 Wu SG, et al. The Mechanism of Acquired Resistance to
Irreversible EGFR Tyrosine Kinase Inhibitor Afatinib in Lung
Adenocarcinoma Patients. Oncotarget. 2016:7(11);12404-13.
9 Rangachari, et al. Brain Metastases in Patients with
EGFR-Mutated or ALK-Rearranged NonSmall-Cell Lung Cancers. Lung
Cancer. 2015;88,108–111
10 Cross DAE, et al. AZD9291, an Irreversible EGFR TKI,
Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung
Cancer. Cancer Discov. 2014:4;1046-61.
11 National Institutes of Health. AZD9291 Versus Placebo in
Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma,
Following Complete Tumour Resection With or Without Adjuvant
Chemotherapy (ADAURA). Available at:
https://www.clinicaltrials.gov/ct2/show/NCT02511106. Accessed
November 2017.
12 National Institutes of Health. AZD9291 in Combination With
Ascending Doses of Novel Therapeutics. Available at:
https://clinicaltrials.gov/ct2/show/NCT02143466. Accessed November
2017.
13 Ramalingam S, et al. Osimertinib vs SoC EGFR-TKI as
First-Line Treatment in Patients with EGFRm Advanced NSCLC
(FLAURA). Presented at the European Society for Medical Oncology
(ESMO) 2017 Congress, 8-12 September 2017, Madrid, Spain.
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