Conversion from accelerated to full approval
confirms the potential of TAGRISSO to become a standard of care for
patients with metastatic EGFR T790M mutation-positive non-small
cell lung cancer whose disease has progressed on or after EGFR-TKI
therapy
Approval based on Phase III AURA3 trial that
demonstrated significant improvement in progression-free survival
with TAGRISSO as compared to chemotherapy
TAGRISSO demonstrated efficacy in patients with
measurable central nervous system (CNS) lesions at baseline
AstraZeneca today announced that the US Food and Drug
Administration (FDA) has granted full approval for TAGRISSO®
(osimertinib) 80mg once-daily tablets, for the treatment of
patients with metastatic epidermal growth factor receptor (EGFR)
T790M mutation-positive non-small cell lung cancer (NSCLC), as
detected by an FDA-approved test, whose disease has progressed on
or after an EGFR tyrosine kinase inhibitor (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, and efficacy data suggest it may be a new standard of
care for these patients.
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said: “By
following the science, we aim to turn lung cancer into a chronic,
manageable disease for patients and this milestone brings us one
step closer to that ambition. The FDA’s full approval reinforces
the potential of TAGRISSO to become the standard of care for
patients with metastatic EGFR T790M mutation-positive non-small
cell lung cancer whose disease has progressed on or after
first-generation EGFR-TKI therapy.”
The full approval in the US is based on data from the
randomized, Phase III AURA3 trial, in which TAGRISSO significantly
improved progression-free survival (PFS) versus platinum-based
doublet chemotherapy, providing 10.1 months of median PFS compared
to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk
reduction; 95% Confidence Interval [CI]: 0.23; 0.41; P<0.001).
The results of this trial were recently presented at the 17th World
Conference on Lung Cancer (WCLC) in Vienna, Austria, and published
in The New England Journal of Medicine.
Additionally, in a post-hoc subgroup analysis of patients with
measurable central nervous system (CNS) lesions, TAGRISSO
demonstrated an objective response rate (ORR) of 57% (95% CI: 37%;
75%) compared to 25% ORR from chemotherapy (95% CI: 7%; 52%). For
CNS patients receiving TAGRISSO, median duration of response (DoR),
defined as the time from the date of first documented response
until progression or death event, was not yet reached at the time
of analysis. Central nervous system metastases are typically
difficult to treat, carry a very poor prognosis and affect up to
40% of patients with NSCLC.
In AURA3 the most common (>20%) adverse reactions observed in
TAGRISSO-treated patients were diarrhea (41%), rash (34%), dry skin
(23%), nail toxicity (22%), and fatigue (22%). Dose reductions
occurred in 2.9% of patients treated with TAGRISSO. The most
frequent adverse reactions that led to dose reductions or
interruptions were prolongation of the QT interval as assessed by
ECG (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious
adverse reactions were reported in 18% of patients treated with
TAGRISSO and 26% of patients in the chemotherapy group. No single
serious adverse reaction was reported in 2% or more patients
treated with TAGRISSO.
H. Jack West, MD, Medical Oncology, Medical Director, Thoracic
Oncology Program, Swedish Cancer Institute, said: “While most lung
cancer specialists have already been very impressed with their
earlier experience with osimertinib and embraced the opportunity to
use it for T790M mutation-positive patients with acquired
resistance to EGFR-TKI therapy, AURA3 provides even more compelling
evidence. Here, we saw a striking efficacy benefit in favor of
osimertinib over chemotherapy in T790M mutation-positive patients.
Testing for EGFR T790M should be a critical next step in patients
who develop acquired resistance after first-line EGFR TKI
therapy.”
TAGRISSO was granted Fast Track, Breakthrough Therapy and
Priority Review designations by the US FDA, and received
Accelerated Approval for this indication in 2015 based on tumor
response rate and duration of response. In September 2016, the FDA
approved a blood-based companion diagnostic, representing the only
FDA-approved and clinically-validated companion diagnostic test
that uses a blood sample to confirm the presence of a T790M
mutation. Blood-based testing is recommended only when a tumor
biopsy cannot be obtained; if a patient tests negative for the
T790M mutation with the blood-based test, their physician should
re-evaluate the feasibility of tissue-based testing.
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%)
INDICATION
TAGRISSO is indicated for the treatment of patients with
metastatic epidermal growth factor receptor (EGFR)
T790M mutation-positive non-small cell lung cancer
(NSCLC), as detected by an FDA-approved test, whose
disease has progressed on or after EGFR tyrosine kinase inhibitor
therapy.
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 26% of all cancer deaths in the US,
and more than breast, prostate and colorectal cancers combined.
Among patients with non-small cell lung cancer (NSCLC), up to 40%
have brain metastases at some time in the course of their disease.
Patients who have EGFR mutation-positive NSCLC, which occurs in 10%
to 15% of NSCLC patients in the US and Europe and 30% to 40% of
NSCLC patients in Asia, are particularly sensitive to treatment
with currently-available EGFR-TKIs, which block the cell signaling
pathways that drive the growth of tumor cells. However, tumors
almost always develop resistance to treatment, leading to disease
progression. Approximately two-thirds of patients develop
resistance to approved EGFR-TKIs such as gefitinib and erlotinib
due to the secondary mutation, T790M.
About TAGRISSO® (osimertinib)
TAGRISSO® (osimertinib) 40mg and 80mg once daily oral tablet has
been approved in over 45 countries, including the US, EU, Japan and
China, for patients with EGFR T790M mutation-positive advanced
non-small cell lung cancer (NSCLC). Eligibility for treatment
with TAGRISSO is dependent on confirmation that the EGFR T790M
mutation is present in the tumor.
TAGRISSO is a third generation, irreversible EGFR tyrosine
kinase inhibitor designed to inhibit both EGFR sensitizing and EGFR
T790M resistance mutations and to have activity in the central
nervous system (CNS). TAGRISSO is also being investigated in
the adjuvant and metastatic first-line settings, including in
patients with and without CNS metastases, in leptomeningeal
metastases, and in combination with other treatments.
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 six
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.
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