28% of patients in the global FLAURA trial
were still receiving TAGRISSO at three years vs. 9% on either
gefitinib or erlotinib
TAGRISSO showed a 52% reduction in risk of
central nervous system disease progression or death
AstraZeneca today presented
detailed overall survival (OS) results from the Phase III FLAURA
trial of TAGRISSO® (osimertinib) 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).
Results showed a statistically significant and clinically
meaningful improvement in OS, a key secondary endpoint for TAGRISSO
versus gefitinib or erlotinib, both of which were previous
standard-of-care (SoC) treatments in this setting (HR 0.799 [95%
CI, 0.641-0.997], p=0.0462).
TAGRISSO delivered a median OS of 38.6 months versus 31.8 months
for the comparator arm. At three years, 28% of patients in the
TAGRISSO arm and 9% of patients in the comparator arm remained on
1st-line study treatment. TAGRISSO also showed a statistically
significant and clinically meaningful 52% reduction in the risk of
central nervous system (CNS) disease progression, increasing the
time patients with CNS metastases lived without CNS disease
progression or death (HR 0.48 [95% CI, 0.26-0.86], p=0.014).1
The results were presented at the Presidential Symposium of the
ESMO (European Society for Medical Oncology) 2019 Congress in
Barcelona, Spain (Abstract #LBA5_PR).
José Baselga, Executive Vice
President, Oncology R&D said: “TAGRISSO has set a new benchmark
in EGFR-mutated non-small cell lung cancer by demonstrating a
median overall survival of more than three years. We have not
before seen survival benefits of this magnitude in any global Phase
III trial with any such therapy. The ground-breaking data reaffirm
the benefit of using TAGRISSO first and further support its use as
the 1st-line standard of care in this setting.”
Dr. Suresh S. Ramalingam,
Principal Investigator of the FLAURA trial from Winship Cancer
Institute of Emory University, Atlanta, US, said: “The results of
the FLAURA trial provide further evidence to support the role of
osimertinib as the preferred 1st-line therapy option for patients
with EGFR-mutated non-small cell lung cancer. It is highly
noteworthy that 28% of patients are still being treated with
1st-line osimertinib at three years versus 9% on either gefitinib
or erlotinib.”
Summary of FLAURA results
TAGRISSO
(n=279)
EGFR-tyrosine kinase
inhibitors (TKI) (gefitinib or erlotinib)
(n=277)
Progression-free survival (PFS)
(primary endpoint)i
Median in months
(95% CI)
18.9
(15.2, 21.4)
10.2 months
(9.6, 11.1)
Hazard ratio
(95% CI)
0.46
(0.37, 0.57)
p-value
p < 0.0001
OS (secondary endpoint)i
Hazard ratio
(95% CI)
0.799
(0.641-0.997)
p-value
p = 0.0462ii
Median in months
(95% CI)
38.6
(34.5-41.8)
31.8
(26.6-36.0)
Survival at 12 months
(95% CI)
89.1%
(84.8-92.2)
82.5%
(77.4-86.6)
Survival at 24 months
(95% CI)
74.2%
(68.6-79.0)
58.9%
(52.7-64.6)
Survival at 36 months
(95% CI)
53.7%
(47.5-59.5)
44.1%
(38.0-50.1)
CNS PFS (secondary endpoint)I,
1
Hazard ratio
(95% CI)
0.48
(0.26-0.86)
p-value
p = 0.014
Median in months
(95% CI)
Not reached
(16.5-NC)iii
13.9
(8.3-NC)iii
Time to first subsequent therapy or
death (TFST) (exploratory endpoint)i
Hazard ratio
(95% CI)
0.48
(0.39-0.58)
Number (%) of patients with events
69.5%
87.4%
Median in months
(95% CI)
25.5
(22.0, 29.1)
13.7
(12.3, 15.7)
Time to second subsequent therapy or
death (TSST) (exploratory endpoint)i
Hazard ratio
(95% CI)
0.69
(0.56-0.84)
Number (%) of patients with events
64.5%
73.3%
Median in months
(95% CI)
31.1
(28.8, 35.9)
23.4
(20.0, 25.6)
Patients remaining on initial study
treatment
12 months
69.5%
47.3%
24 months
42.3%
16.2%
36 months
28.0%
9.4%
I The data cut-off date was 25 June 2019 (OS, TFST, TSST) and 12
June 2017 (PFS, CNS PFS) ii Criteria for statistical significance
at the final analysis of OS was a p-value of less than 0.0495
(determined by O’Brien- Fleming approach) iii NC=Not Calculable
In the FLAURA trial, the safety and tolerability of TAGRISSO was
consistent with its established profile. TAGRISSO was generally
well tolerated, with Grade 3 or higher adverse events (AEs)
occurring in 42% of patients taking TAGRISSO versus 47% in the
comparator arm. The most common AEs in patients treated with
TAGRISSO were diarrhea (60%), rash (59%), nail toxicity (39%), dry
skin (38%), stomatitis (29%), fatigue (21%) and decreased appetite
(20%). Despite almost twice the length of therapy, fewer patients
experienced a grade 3 or higher AE (42% vs. 47%) or discontinued
due to AEs (15% vs. 18%).
The FLAURA trial met its
primary endpoint in July 2017, showing a statistically significant
and clinically meaningful improvement in PFS, increasing the time
patients lived without disease progression or death from any
cause.
TAGRISSO is currently approved in 78 countries, including the
US, Japan, China and the EU, for 1st-line EGFR-mutated (EGFRm)
metastatic NSCLC.
TAGRISSO IMPORTANT SAFETY INFORMATION
TAGRISSO may cause serious side effects, including:
- lung problems. TAGRISSO may cause lung problems that may
lead to death. Symptoms may be similar to symptoms from lung
cancer. Tell your doctor right away if you have any new or
worsening lung symptoms, including trouble breathing, shortness of
breath, cough, or fever
- heart problems, including heart failure. TAGRISSO may
cause heart problems that may lead to death. Your doctor should
check your heart function before you start taking TAGRISSO and
during treatment as needed. Tell your doctor right away if you have
any of the following signs and symptoms of a heart problem: feeling
like your heart is pounding or racing, shortness of breath,
swelling of your ankles and feet, feeling lightheaded
- eye problems. TAGRISSO may cause eye problems. Tell your
doctor right away if you have symptoms of eye problems which may
include watery eyes, sensitivity to light, eye pain, eye redness,
or vision changes. Your doctor may send you to see an eye
specialist (ophthalmologist) if you get eye problems with
TAGRISSO
Before taking TAGRISSO, tell your doctor about all of your
medical conditions, including if you:
- have lung or breathing problems
- have heart problems, including a condition called long QTc
syndrome
- have problems with your electrolytes, such as sodium,
potassium, calcium or magnesium
- have a history of eye problems
- are pregnant or plan to become pregnant. TAGRISSO can harm your
unborn baby. Tell your doctor right away if you become pregnant
during treatment with TAGRISSO or think you may be pregnant
- Females who are able to become pregnant should use
effective birth control during treatment with TAGRISSO and for 6
weeks after the final dose of TAGRISSO
- Males who have female partners that are able to become
pregnant should use effective birth control during treatment with
TAGRISSO and for 4 months after the final dose of TAGRISSO
- are breastfeeding or plan to breastfeed. It is not known if
TAGRISSO passes into your breast milk. Do not breastfeed during
treatment with TAGRISSO and for 2 weeks after your final dose of
TAGRISSO. Talk to your doctor about the best way to feed your baby
during this time
Tell your doctor about all the medicines you take, including
prescription and over-the-counter medicines, vitamins, or herbal
supplements. Especially tell your doctor if you take a heart or
blood pressure medicine
The most common side effects of TAGRISSO are:
- diarrhea
- rash
- dry skin
- changes in your nails, including: redness, tenderness, pain,
inflammation, brittleness, separation from nailbed, and shedding of
nails
- mouth sores
- tiredness
- decreased appetite
Tell your doctor if you have any side effect that bothers you or
that does not go away.
These are not all the possible side effects of TAGRISSO. For
more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
What is TAGRISSO?
TAGRISSO is a prescription medicine for non-small cell lung
cancer (NSCLC) that has spread to other parts of the body
(metastatic). TAGRISSO is used:
- as a first treatment if tumors have a certain abnormal
epidermal growth factor receptor (EGFR) gene(s)
or
- for a certain type of EGFR gene that has been treated with an
EGFR tyrosine kinase inhibitor (TKI) medicine that did not work or
is no longer working
Your doctor will perform a test to make sure that TAGRISSO is
right for you.
It is not known if TAGRISSO is safe and effective in
children.
Please see full Prescribing Information including Patient
Information.
NOTES TO EDITORS
About 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,
more than breast, prostate and colorectal cancers combined.2 Lung
cancer is broadly split into NSCLC and small cell lung cancer
(SCLC), with 80-85% classified as NSCLC.3 Approximately 10-15% of
NSCLC patients in the US and Europe, and 30-40% of patients in Asia
have EGFRm NSCLC.4-6 These patients are particularly sensitive to
treatment with EGFR-TKIs which block the cell-signaling pathways
that drive the growth of tumor cells. Approximately 25% of patients
with EGFRm NSCLC have brain metastases at diagnosis, increasing to
approximately 40% within two years of diagnosis.7 The presence of
brain metastases often reduces median survival to less than eight
months.8
About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible
EGFR-TKI designed to inhibit both EGFR-sensitizing and EGFR
T790M-resistance mutations, with clinical activity against CNS
metastases. TAGRISSO 40mg and 80mg once-daily oral tablets have now
received approval in more than 75 countries, including the US,
Japan, China and the EU, for 1st-line EGFRm advanced NSCLC, and in
more than 85 countries, including the US, Japan, China and the EU,
for 2nd-line use in patients with EGFR T790M mutation-positive
advanced NSCLC. TAGRISSO is also being developed in the adjuvant
setting (ADAURA trial), in the locally-advanced unresectable
setting (LAURA), in combination with chemotherapy (FLAURA2) in the
metastatic setting, and with potential new medicines to address
resistance to EGFR-TKIs (SAVANNAH, ORCHARD).
About FLAURA
The FLAURA trial assessed the efficacy and safety of TAGRISSO
80mg orally once daily vs. comparator EGFR-TKIs (either gefitinib
[250mg orally, once daily] or erlotinib [150mg orally, once daily])
in previously-untreated patients with locally-advanced or
metastatic EGFRm NSCLC. The trial was double-blinded and
randomized, with 556 patients across 29 countries.
About AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and
potential new medicines in late-stage clinical development for the
treatment of different forms of lung cancer spanning several stages
of disease, lines of therapy and modes of action. We aim to address
the unmet needs of patients with EGFR-mutated tumors as a genetic
driver of disease, which occur in 10-15% of NSCLC patients in the
US and EU and 30-40% of NSCLC patients in Asia, with our approved
medicines gefitinib and TAGRISSO, and ongoing Phase III trials
ADAURA, LAURA and FLAURA2 as well as the Phase II combination
trials SAVANNAH and ORCHARD.4-6
Our extensive late-stage Immuno-Oncology program focuses on lung
cancer patients without a targetable genetic mutation which
represents approximately three-quarters of all patients with lung
cancer.9 Durvalumab, an anti-PDL1 antibody, is in development for
patients with advanced disease (Phase III trials POSEIDON, PEARL,
and CASPIAN) and for patients in earlier stages of disease
including potentially-curative settings (Phase III trials AEGEAN,
PACIFIC-2, ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5) both
as monotherapy and in combination with tremelimumab and/or
chemotherapy.
About AstraZeneca in oncology
AstraZeneca 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, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca’s main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates – and by championing the development
of personalized combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three therapy areas – Oncology, Cardiovascular, Renal and
Metabolism (CVRM) and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca-us.com and follow us
on Twitter @AstraZenecaUS
References
1. Vansteenkiste J, et al. CNS Response to Osimertinib vs
Standard of Care (SoC) EGFR-TKI as First-line Therapy in Patients
(pts) with EGFR-TKI Sensitising Mutation (EGFRm)-positive Advanced
Non-Small Cell Lung Cancer (NSCLC): Data from the FLAURA Study.
Annals of Oncology. 2017:28(10);189 [Accessed September 2019]. 2.
World Health Organization. International Agency for Research on
Cancer. Globocan Worldwide Fact Sheet 2018. Available at
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx [Accessed
September 2019]. 3. LUNGevity Foundation. Types of Lung Cancer.
Available at
https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer
[Accessed September 2019]. 4. 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 [Accessed September 2019]. 5. 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 [Accessed September 2019]. 6. 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 [Accessed September 2019]. 7.
Rangachari, et al. Brain Metastases in Patients with EGFR-Mutated
or ALK-Rearranged Non-Small-Cell Lung Cancers. Lung Cancer.
2015;88,108–111 [Accessed September 2019]. 8. Ali A, et al.
Survival of Patients with Non-small-cell Lung Cancer After a
Diagnosis of Brain Metastases. Curr Oncol. 2013;20(4):e300-e306
[Accessed September 2019]. 9. Pakkala, S, et al. Personalized
therapy for lung cancer: striking a moving target. JCI Insight.
2018;3(15):e120858.
US-30868 Last Updated 9/19
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