REG - AstraZeneca PLC - Tagrisso plus chemo approved in US for lung cancer

AstraZenecaAnnouncement

19/02/2024 07:15

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RNS Number : 5215D  AstraZeneca PLC  19 February 2024

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
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-granted-priority-review-us-patients-egfr-mutated-advanced-lung-cancer.html)
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
(https://www.nejm.org/doi/full/10.1056/NEJMoa2306434) . 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
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-demonstrated-strong-overall-survival-benefit-in-the-adaura-phase-iii-trial.html)
and late-stage disease in the FLAURA Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2019/tagrisso-significantly-improves-overall-survival-in-the-phase-iii-flaura-trial-for-1st-line-egfr-mutated-non-small-cell-lung-cancer-09082019.html)
and FLAURA2 Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-extended-median-progression-free-survival-by-nearly-9-months-in-egfr-mutated-advanced-lung-cancer-in-flaura2-phase-iii-trial.html)
.

 

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 (http://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

Contacts

For details on how to contact the Investor Relations Team, please click here.
For Media contacts, click here
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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

 

 

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