WILMINGTON, Del.--(BUSINESS WIRE)--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 III FLAURA trial, 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 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.
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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 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
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 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-15760 Last Updated 12/17
