Market Overview

TAGRISSO® (osimertinib) Receives US FDA Full Approval


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
  • 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%)


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
 including Patient Information.


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

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
and follow us on Twitter @AstraZenecaUS.

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