19 February 2024
Tagrisso with the
addition of chemotherapy approved in the
US for patients with EGFR-mutated advanced
lung cancer
Approval based on FLAURA2 results which showed
Tagrisso plus chemotherapy extended
median progression-free survival by nearly 9 months vs. standard of
care
AstraZeneca's Tagrisso (osimertinib) with the
addition of chemotherapy has been approved in the US for
the treatment of adult patients with locally
advanced or metastatic epidermal growth factor receptor-mutated
(EGFRm) non-small cell lung cancer (NSCLC).
The approval following a
Priority Review by the Food and Drug
Administration (FDA) was based on the results from the
FLAURA2 Phase III trial published in The New
England Journal of Medicine. Tagrisso with the
addition of chemotherapy reduced the risk of disease progression or
death by 38% compared to Tagrisso monotherapy which is the
1st-line global standard of care (hazard ratio [HR] 0.62; 95%
confidence interval [CI] 0.49-0.79; p<0.0001). Median
progression-free survival (PFS) by investigator assessment was 25.5
months for patients treated with Tagrisso plus chemotherapy, an
8.8-month improvement versus Tagrisso monotherapy (16.7
months).
PFS results from blinded independent central
review (BICR) were consistent with the results by investigator
assessment, showing 29.4 months median PFS with Tagrisso plus chemotherapy, a
9.5-month improvement over Tagrisso monotherapy (19.9 months) (HR
0.62; 95% CI 0.48-0.80; p=0.0002).
Each year in the US, there are over
200,000 people diagnosed with lung cancer, and 80-85% of these
patients are diagnosed with NSCLC, the most common form of lung
cancer.1-3 Approximately 70% of people are diagnosed
with advanced NSCLC.4 Additionally, about 15% of NSCLC
patients in the US have an EGFR mutation.5
Pasi A. Jänne, MD, PhD, medical oncologist at
Dana-Farber Cancer Institute and principal investigator for the
trial, said: "This approval based on the unprecedented
data from FLAURA2 brings a critical new treatment option to
patients with advanced EGFR-mutated non-small cell lung cancer.
Now, with the choice of two highly effective osimertinib-based
options, physicians can better tailor treatment to an individual's
needs and help ensure the best possible outcome for each
patient."
Dave Fredrickson, Executive Vice
President, Oncology Business Unit,
AstraZeneca, said: "This important new
treatment option can delay disease progression by nearly nine
additional months, establishing a new benchmark with the longest
reported progression-free survival benefit in the 1st-line advanced
setting. This approval reinforces Tagrisso as the backbone of
EGFR-mutated lung cancer treatment either as monotherapy or in
combination with chemotherapy. This news is especially important
for those with a poorer prognosis, including patients whose cancer
has spread to the brain and those with L858R mutations."
Laurie Ambrose, President and CEO, GO2 for Lung
Cancer, said: "We are so excited to see this continued progress
advancing more personalized treatment options for our community.
The more we can target the right treatments for the right people at
the right time, the better outcomes will be for our community - a
goal we all collectively share."
Results from a prespecified exploratory
analysis of patients in the FLAURA2 trial with brain metastases at
baseline showed Tagrisso
plus chemotherapy reduced the risk of central nervous system (CNS)
disease progression or death by 42% compared to Tagrisso alone (HR 0.58; 95% CI
0.33-1.01) as assessed by BICR. With two years of follow up, 74% of
patients treated with Tagrisso plus chemotherapy had not
experienced CNS disease progression or death versus 54% of patients
treated with Tagrisso
monotherapy.
While the overall survival (OS) results
remained immature at the second interim analysis (41% maturity), no
trend towards a detriment was observed (HR 0.75; 95% CI 0.57-0.97).
The trial continues to assess OS as a key secondary
endpoint.
The safety profile of Tagrisso with
the addition of chemotherapy was generally
manageable and consistent with the established profiles of the
individual medicines. Adverse event (AE) rates were higher in
the Tagrisso plus
chemotherapy arm, driven by well-characterised chemotherapy-related
AEs. Discontinuation rates for Tagrisso due to AEs were low in both
arms of the trial (11% for Tagrisso plus chemotherapy and 6% for
monotherapy).
In December 2023, osimertinib
(Tagrisso) with the
addition of chemotherapy was added to the NCCN Clinical Practical
Guidelines in Oncology (NCCN Guidelines®) as a NCCN Category 1
Other Recommended regimen for patients with NSCLC whose tumours
have EGFR exon 19 deletion or exon 21 L858R mutations based on the
data from FLAURA2.6
The US regulatory submission was
reviewed under Project Orbis, which provides a
framework for concurrent submission and review of oncology
medicines among participating international partners. As part of
Project Orbis, Tagrisso in combination with
chemotherapy is also under review by regulatory authorities in
Australia, Canada, and Switzerland. Regulatory applications
are also under review in several other countries based on the
FLAURA2 results.
Tagrisso is approved as
monotherapy in more than 100 countries including in the US, EU,
China and Japan. Approved indications include for 1st-line
treatment of patients with locally advanced or metastatic EGFRm
NSCLC, locally advanced or metastatic EGFR T790M mutation-positive
NSCLC, and adjuvant treatment of early-stage EGFRm
NSCLC.
As part of AstraZeneca's ongoing
commitment to treating patients as early as possible in lung
cancer, Tagrisso is also
being investigated in the neoadjuvant setting in the NeoADAURA
Phase III trial with results expected later this year, and in the
early-stage adjuvant resectable setting in the ADAURA2 Phase III
trial.
Notes
Lung cancer
Lung cancer is the leading cause of
cancer death among both men and women, accounting for about
one-fifth of all cancer deaths.7 Lung cancer is broadly
split into NSCLC and small cell lung cancer.2 The
majority of all NSCLC patients are diagnosed with advanced
disease.4
Patients with EGFRm NSCLC are
particularly sensitive to treatment with an EGFR-tyrosine kinase
inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that
drive the growth of tumour cells.8
FLAURA2
FLAURA2 is a randomised, open-label,
multi-centre, global Phase III trial in the 1st-line treatment of
patients with locally advanced (Stage IIIB-IIIC) or metastatic
(Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once daily oral tablets
with the addition of chemotherapy (pemetrexed (500mg/m2) plus
cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for
four cycles, followed by Tagrisso with pemetrexed maintenance
every three weeks.
The trial enrolled 557 patients in
more than 150 centres across more than 20 countries, including in
the US, Europe, South America and Asia. The primary endpoint is
PFS. The trial is ongoing and will continue to assess the secondary
endpoint of OS.
Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI
with proven clinical activity in NSCLC, including against CNS
metastases. Tagrisso (40mg
and 80mg once-daily oral tablets) has been used to treat more than
800,000 patients across its indications worldwide and AstraZeneca
continues to explore Tagrisso as a treatment for patients
across multiple stages of EGFRm NSCLC.
There is an extensive body of
evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy
to improve patient outcomes in both early-stage disease in
the
ADAURA Phase III trial and late-stage
disease in the
FLAURA Phase III trial and
FLAURA2 Phase III trial.
The Company is also researching ways
to address tumour mechanisms of resistance through the SAVANNAH and
ORCHARD Phase II trials, and the SAFFRON Phase III trial, which
test Tagrisso plus
savolitinib, an oral, potent and highly selective MET TKI, as well
as other potential new medicines.
AstraZeneca in lung
cancer
AstraZeneca is working to bring
patients with lung cancer closer to cure through the detection and
treatment of early-stage disease, while also pushing the boundaries
of science to improve outcomes in the resistant and advanced
settings. By defining new therapeutic targets and investigating
innovative approaches, the Company aims to match medicines to the
patients who can benefit most.
The Company's comprehensive
portfolio includes leading lung cancer medicines and the next wave
of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and
datopotamab deruxtecan in collaboration with Daiichi Sankyo;
Orpathys (savolitinib) in
collaboration with HUTCHMED; as well as a pipeline of potential new
medicines and combinations across diverse mechanisms of
action.
AstraZeneca is a founding member of
the Lung Ambition Alliance, a global coalition working to
accelerate innovation and deliver meaningful improvements for
people with lung cancer, including and beyond treatment.
AstraZeneca in oncology
AstraZeneca is leading a revolution
in oncology with the ambition to provide cures for cancer in every
form, following the science to understand cancer and all its
complexities to discover, develop and deliver life-changing
medicines to patients.
The Company's focus is on some of
the most challenging cancers. It is through persistent innovation
that AstraZeneca has built one of the most diverse portfolios and
pipelines in the industry, with the potential to catalyse changes
in the practice of medicine and transform the patient
experience.
AstraZeneca has the vision to
redefine cancer care and, one day, eliminate cancer as a cause of
death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is
a global, science-led biopharmaceutical company that focuses on the
discovery, development, and commercialisation of prescription
medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please visit astrazeneca.com
and follow the Company on social media
@AstraZeneca.
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References
1. ASCO. Lung Cancer -
Non-Small Cell: Introduction. Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment.
Accessed February 2024.
2. LUNGevity Foundation.
Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed February
2024.
3. American Cancer
Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html#:~:text=About%2080%25%20to%2085%25%20of,(outlook)%20are%20often%20similar.
Accessed February
2024.
4. Cagle PT,
et al. Lung Cancer
Biomarkers: Present Status and Future Developments. Archives
Pathology Lab Med.
2013;137:1191-1198.
5. Keedy VL,
et al. American Society of
Clinical Oncology Provisional Clinical Opinion: Epidermal Growth
Factor Receptor (EGFR) Mutation Testing for Patients with Advanced
Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine
Kinase Inhibitor Therapy. J Clin
Oncol. 2011:29;2121-27.
6. NCCN, National Comprehensive
Cancer Network® (NCCN®). Referenced with permission from the NCCN
Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for
Non-Small Cell Lung Cancer Version 1.2024.© National Comprehensive
Cancer Network, Inc. [2024]. All rights reserved. Accessed
[February 14, 2024]. To view the most recent and complete version
of the guideline, go online to NCCN.org. NCCN makes no warranties
of any kind whatsoever regarding their content, use or application
and disclaims any responsibility for their application or use in
any way.
7. World Health
Organisation. International Agency for Research on Cancer. Lung
Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed February 2024.
8. Cross
DA, et al. AZD9291, an
Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR
Inhibitors in Lung Cancer. Cancer
Discov. 2014;4(9):1046-1061.
Adrian Kemp
Company Secretary
AstraZeneca PLC