Market Overview

US FDA Accepts Regulatory Submission for TAGRISSO (Osimertinib) in 1st-Line EGFR-Mutated Non-Small Cell Lung Cancer


TAGRISSO granted Priority Review; acceptance follows FDA's
Breakthrough Therapy Designation

AstraZeneca today announced that the US Food and Drug Administration
(FDA) has accepted a supplemental New Drug Application (sNDA) for the
use of TAGRISSO® (osimertinib), a third-generation,
irreversible epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitor (TKI) with clinical activity against central nervous system
(CNS) metastases, in the 1st-line treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors have EGFR mutations
(exon 19 deletions or exon 21 (L858R) substitution mutations). The FDA
has granted TAGRISSO Priority Review status, and previously granted Breakthrough
Therapy Designation
for TAGRISSO in the 1st-line treatment of
patients with metastatic EGFR mutation-positive (EGFRm) NSCLC.

The submission acceptance is based on data from the Phase
, in which TAGRISSO significantly improved
progression-free survival (PFS) compared to current 1st-line EGFR-TKIs,
erlotinib or gefitinib, in previously-untreated patients with locally
advanced or metastatic EGFRm NSCLC.

Detailed results of the FLAURA trial can be found in the New
England Journal of Medicine
, published November 18, 2017.

On September 28, 2017, the US NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) were updated to include the use
of TAGRISSO in the 1st-line treatment of patients with locally
advanced or metastatic EGFRm NSCLC. The use of TAGRISSO in this
indication is not yet approved by the FDA.

TAGRISSO once-daily tablets are approved by the 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® (osimertinib) Important Safety

  • 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 (e.g., 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%)

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 one-quarter of all cancer deaths, more than breast, prostate and
colorectal cancers combined. Approximately 7% to 23% in Western
populations and 30% to 50% of patients in Asian populations have tumors
that contain activating mutations in epidermal growth factor receptor
(EGFR). 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 also targets this
secondary mutation that leads to disease progression. There is also a
need for medicines with improved central nervous system efficacy, since
approximately 25% of patients with EGFR-mutated NSCLC have brain
metastases at 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 60
countries, including the US, EU, Japan and China, for patients with EGFR
T790M mutation-positive advanced non-small cell lung cancer.

TAGRISSO is also being investigated in the adjuvant setting and in
combination with other treatments.

About the FLAURA trial
The FLAURA trial assessed the
efficacy and safety of osimertinib 80mg 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 trial, with 556
patients across 29 countries.

About AstraZeneca in Lung Cancer
AstraZeneca 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 tumor 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 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

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 &
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
and follow us on Twitter @AstraZenecaUS.

US-15760 Last Updated 12/17

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