Market Overview

TAGRISSO® (osimertinib) Granted Breakthrough Therapy Designation by US FDA for the 1st-Line Treatment of Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer


Designation based on positive Phase III FLAURA trial results

Sixth Breakthrough Therapy Designation for an AstraZeneca New
Oncology medicine

AstraZeneca today announced that the US Food and Drug Administration
(FDA) has granted Breakthrough Therapy Designation (BTD) for TAGRISSO®
(osimertinib) for the 1st-line treatment of patients with metastatic
epidermal growth factor receptor (EGFR) mutation-positive non-small cell
lung cancer (NSCLC).

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: "The Breakthrough
Designation acknowledges not only TAGRISSO's potential as a 1st-line
standard of care in advanced EGFR mutation-positive NSCLC, but also the
significant need for improved clinical outcomes in this disease. The
results of the FLAURA trial have the potential to redefine clinical
expectations and offer new hope for patients who currently have a poor

The FDA granted the BTD based on data from the Phase III FLAURA trial of
osimertinib versus standard-of-care EGFR tyrosine kinase
inhibitor (TKI) therapy in previously-untreated patients with
locally-advanced or metastatic EGFR mutation-positive NSCLC. In the
trial, median progression-free survival was 18.9 months for osimertinib
compared with 10.2 months for EGFR-TKIs (erlotinib or gefitinib).
Improvements were seen in all pre-specified subgroups, including
patients with and without brain metastases.

In the FLAURA trial, the safety profile of osimertinib was consistent
with previous experience. 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, 34% had a Grade ≥3 AE, compared to 45% in the comparator
arm, and 13% of patients on osimertinib had an AE leading to treatment
discontinuation compared to 18% in the comparator arm.

On September 28, 2017, the US NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) were updated to include the use
of osimertinib in the 1st-line treatment of patients with
locally-advanced or metastatic EGFR mutation-positive NSCLC. The use of
osimertinib for the first-line treatment of patients with
locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet
FDA approved.

TAGRISSO is currently approved in more than 50 countries, including the
US, EU, Japan and China, as 2nd-line treatment for patients with
advanced NSCLC who progress following treatment with an EGFR-TKI due to
the EGFR T790M resistance mutation. 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
is the first and only approved medicine in the US indicated for NSCLC
patients who have tested positive for the EGFR T790M mutation.

This is the sixth BTD that AstraZeneca has received from the FDA for an
oncology medicine since 2014. BTD is designed to expedite the
development and regulatory review of new medicines that are intended to
treat a serious condition and that have shown encouraging early clinical
results, which demonstrate substantial improvement on a clinically-
significant endpoint over available medicines and when there is
significant unmet medical need.

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 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


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 and
follow us on Twitter @AstraZenecaUS.

US-15411 Last Updated 10/17

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