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 prognosis.”
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
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 (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 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-15411 Last Updated 10/17
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