Phase III FLAURA trial results show TAGRISSO
reduced the risk of progression or death by more than half, with
consistent results across all subgroups, including those with and
without brain metastases
Superior median progression-free survival
(PFS) of 18.9 months compared with 10.2 months for the current
standard of care
Clinically meaningful trend in overall
survival benefit
AstraZeneca today announced the full results of the Phase III
FLAURA trial, which support TAGRISSO®’s (osimertinib) clear
potential as a new standard of care (SoC) 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 of the Phase III FLAURA trial were included at the
Presidential Symposium I of the European Society of Medical
Oncology (ESMO) 2017 Congress in Madrid, Spain, and demonstrate a
superior, clinically-meaningful progression-free survival (PFS)
with osimertinib compared to current SoC EGFR tyrosine kinase
inhibitors (TKIs) (erlotinib or gefitinib).
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said: “The
FLAURA data are truly exciting. Until now, even with the
therapeutic advances offered by the first- and second-generation
EGFR inhibitors, less than 20% of EGFR mutation-positive NSCLC
patients survive for five years. The FLAURA data suggest early and
sustained benefit with TAGRISSO that has the potential to
significantly impact long-term patient outcomes and help address
the considerable unmet need that remains.”
Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA
study, from the Winship Cancer Institute of Emory University,
Atlanta, GA, said: “The FLAURA data are likely to result in a major
paradigm shift in the treatment of patients with EGFR
mutation-positive advanced lung cancer. Not only did the trial
demonstrate a robust improvement in efficacy with osimertinib when
compared to other commonly-used EGFR inhibitors, the side effects
profile was also more favorable with osimertinib.”
Summary of key results:
Endpoint
TAGRISSO SoC Hazard ratio
(HR)/Odds ratio (OR) PFS(primary endpoint)
18.9 months(median)
10.2 months(median)
HR 0.4695% CI, 0.37-0.57, p<0.0001
Overall Survival (OS)at 25% maturity
N/A N/A HR 0.6395% CI, 0.45-0.88, p=0.0068*
Duration ofResponse (DoR)
17.2 months(median)
8.5 months(median)
N/A
Objective ResponseRate (ORR)
80% 76% OR 1.280.85-1.93, p=0.2335
*0.0015 was the threshold required for statistical significance
at the current level of maturity. A final OS analysis is planned at
a later stage.
Highlights from the FLAURA data presented include:
- Superior PFS
(primary endpoint): Patients on osimertinib had less than
half the risk of progression or death compared to patients on
erlotinib or gefitinib (hazard ratio [HR] 0.46; 95% confidence
interval [CI] 0.37, 0.57; p<0.0001). The median PFS was 18.9
months for patients on osimertinib vs. 10.2 months for patients in
the comparator arm.
- Clinically
meaningful preliminary overall survival (OS) data at 25%
maturity: The hazard ratio for OS was 0.63 [95% CI: 0.45,
0.88; P=0.0068] favoring osimertinib. OS data were 25% mature at
the time of the interim analysis. (21% of the patients on
osimertinib had died and 30% of the patients on the comparator arm
had died.) The p-value of 0.0068 was not below the threshold of
0.0015 required for statistical significance at the current level
of maturity. A final OS analysis is planned at a later stage.
- PFS improvements
consistent across subgroups: Improvements in PFS with
osimertinib were consistent across all pre-specified patient
subgroups, with at least a 40% reduction in the risk of progression
or death, including in patients with/without central nervous system
(CNS) metastases at study entry, Asian/non-Asian patients, patients
with/without prior smoking history, and patients with Exon 19
deletion/L858R sensitizing mutations.
- Impressive
duration of response (DoR) and objective response rate
(ORR): Patients treated with osimertinib had more than
double the median DoR than those on the comparator arm (17.2 months
vs. 8.5 months), and an ORR (a measurement of tumor shrinkage) of
80% vs. 76% with the comparator arm [odds ratio 1.28 (0.85, 1.93),
p=0.2335].
The FLAURA safety data for osimertinib was in line with that
observed in prior clinical trials, with a low rate of Grade ≥3
adverse events (AEs). In patients treated with osimertinib, the
most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and
dry skin (32%, any grade [<1% Grade ≥3]), and in the comparator
arm group the most common AEs were diarrhea (57%, any grade [2%
Grade ≥3]) and dermatitis acneiform (48%, any grade [5% Grade ≥3]).
Of the patients on osimertinib, 33.7% had a Grade ≥3 AE, compared
to 44.8% in the comparator arm, and 13.3% of patients on
osimertinib had an AE leading to treatment discontinuation compared
to 18.1% in the comparator arm.
This indication is not yet FDA approved. AstraZeneca is in
discussions with global health authorities regarding regulatory
submissions for osimertinib based on the FLAURA data. A status of
regulatory submissions is usually provided with the Company’s
quarterly results announcement.
TAGRISSO once-daily tablets are approved by the US Food and Drug
Administration (FDA) for the treatment of patients with metastatic
EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved
test, whose disease has progressed on or after an EGFR TKI therapy.
TAGRISSO is the first and only approved medicine in the US
indicated for NSCLC patients who have tested positive for the EGFR
T790M mutation.
TAGRISSO® (osimertinib) Important Safety
Information
- There are no contraindications for
TAGRISSO
- Interstitial Lung Disease
(ILD)/Pneumonitis occurred in 3.5% and was fatal in 0.6% of 833
TAGRISSO-treated patients. Withhold TAGRISSO and promptly
investigate for ILD in patients who present with worsening of
respiratory symptoms indicative of ILD (eg, dyspnea, cough,
and fever). Permanently discontinue TAGRISSO if ILD is
confirmed
- Heart rate-corrected QT (QTc) interval
prolongation occurred in TAGRISSO-treated patients. Of the 833
TAGRISSO-treated patients, 0.7% of patients were found to have a
QTc > 500 msec, and 2.9% of patients had an increase from
baseline QTc > 60 msec. No QTc-related arrhythmias were
reported. Conduct periodic monitoring with ECGs and electrolytes in
patients with congenital long QTc syndrome, congestive heart
failure, electrolyte abnormalities, or those who are taking
medications known to prolong the QTc interval. Permanently
discontinue TAGRISSO in patients who develop QTc interval
prolongation with signs/symptoms of life-threatening
arrhythmia
- Cardiomyopathy occurred in 1.9% and was
fatal in 0.1% of 833 TAGRISSO-treated patients. Left Ventricular
Ejection Fraction (LVEF) decline ≥ 10% and a drop to < 50%
occurred in 4% of 655 TAGRISSO-treated patients. Conduct cardiac
monitoring, including an assessment of LVEF at baseline and during
treatment in patients with cardiac risk factors. Assess LVEF in
patients who develop relevant cardiac signs or symptoms during
treatment. For symptomatic congestive heart failure or persistent,
asymptomatic LV dysfunction that does not resolve within 4 weeks,
permanently discontinue TAGRISSO
- Keratitis was reported in 0.7% of 833
TAGRISSO-treated patients in clinical trials. Promptly refer
patients with signs and symptoms suggestive of keratitis (such as
eye inflammation, lacrimation, light sensitivity, blurred vision,
eye pain, and/or red eye) to an ophthalmologist
- Advise pregnant women of the potential
risk to a fetus. Advise females of reproductive potential to use
effective contraception during TAGRISSO treatment and for 6 weeks
after the final dose. Advise males with female partners of
reproductive potential to use effective contraception for 4
months after the final dose
- The most common adverse reactions
(≥20%) in patients treated with TAGRISSO were diarrhea (41%), rash
(34%), dry skin (23%), nail toxicity (22%), and fatigue (22%)
Please see complete Prescribing
Information including Patient Information.
NOTES TO EDITORS
About Non-Small Cell Lung Cancer (NSCLC)
Lung 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.
Approximately 10% to 15% of patients in the US and Europe, and 30%
to 40% of patients in Asia have epidermal growth factor receptor
mutation-positive (EGFRm) NSCLC. These patients are particularly
sensitive to treatment with currently-available EGFR tyrosine
kinase inhibitors (TKIs), which block the cell signaling pathways
that drive the growth of tumor cells. However, tumors almost always
develop resistance to EGFR-TKI treatment, leading to disease
progression. Approximately half of patients develop resistance to
approved EGFR-TKIs, such as gefitinib and erlotinib, due to the
resistance mutation, EGFR T790M. TAGRISSO targets this secondary
mutation that leads to disease progression. There is also a need
for agents with improved central nervous system efficacy since
approximately 25% of patients with EGFRm NSCLC have brain
metastases at first diagnosis, increasing to approximately 40%
within two years of diagnosis.
About TAGRISSO® (osimertinib)
TAGRISSO® (osimertinib) is a third-generation, irreversible
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
(TKI) designed to inhibit both EGFR sensitizing and EGFR T790M
resistance mutations, with clinical activity against central
nervous system (CNS) metastases. TAGRISSO 40mg and 80mg once-daily
oral tablets have been approved in more than 50 countries,
including the US, EU, Japan and China, for patients with EGFR T790M
mutation-positive advanced non-small cell lung cancer. Eligibility
for treatment with TAGRISSO is dependent on confirmation that the
EGFR T790M mutation is present in the tumor.
TAGRISSO is also being investigated in the adjuvant and
metastatic 1st-line settings, including in patients with and
without CNS metastases, in leptomeningeal metastases and in
combination with other treatments.
About FLAURA
FLAURA assessed the efficacy and safety of osimertinib 80mg
orally once daily vs. standard-of-care epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitors (TKIs) (either erlotinib
[150mg orally, once daily] or gefitinib [250mg orally, once daily])
in previously untreated patients with locally advanced or
metastatic EGFR mutation-positive non-small cell lung cancer. The
trial was a double-blinded, randomized study, with 556 patients
across 30 countries.
The primary endpoint of the trial was progression-free survival,
and secondary endpoints included overall survival, objective
response rate, duration of response, disease control rate, safety
and measures of health-related quality of life.
About AstraZeneca in Lung Cancer
AstraZeneca is using ground-breaking science to develop a wide
range of medicines for patients with lung cancer. We are pioneering
precision medicines that target molecular mutations in tumor cells,
as well as those that aim to boost the power of the immune response
against cancer. We are committed to transforming outcomes for
patients with lung cancer, whose treatment options are currently
limited.
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, 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 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 main 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-us.com and follow us on Twitter
@AstraZenecaUS.
US-14134 Last Updated 8/17
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