TIDMAZN
RNS Number : 2932O
AstraZeneca PLC
29 May 2020
28 May 2020 22:00 BST
Tagrisso demonstrated unprecedented disease-free survival in the
adjuvant treatment of Stage IB-IIIA patients with EGFR-mutated lung
cancer
Phase III ADAURA trial showed treatment with Tagrisso after
surgery with
curative intent reduced the risk of disease recurrence or death
by c. 80%
Detailed results from the Phase III ADAURA trial showed
AstraZeneca's Tagrisso (osimertinib) demonstrated a statistically
significant and clinically meaningful improvement in disease-free
survival (DFS) in the adjuvant treatment of patients with
early-stage (IB, II and IIIA) epidermal growth factor
receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after
complete tumour resection with curative intent.
Results will be presented during the plenary session of the
American Society of Clinical Oncology ASCO20 Virtual Scientific
Program on 31 May (abstract #LBA5).
In the primary endpoint of DFS in patients with Stage II and
IIIA disease, adjuvant treatment (after surgery) with Tagrisso
reduced the risk of disease recurrence or death by 83% (based on a
hazard ratio [HR] of 0.17; 95% confidence interval [CI] 0.12, 0.23;
p<0.0001). DFS results in the overall trial population, Stage IB
through IIIA, a key secondary endpoint, demonstrated a reduction in
the risk of disease recurrence or death of 79% (based on a HR of
0.21; 95% CI 0.16, 0.28; p<0.0001).
At two years, 89% of patients in the trial treated with Tagrisso
remained alive and disease free versus 53% on placebo. Consistent
DFS results were seen across all subgroups, including patients who
were treated with surgery followed by chemotherapy and those who
received surgery only, as well as in Asian and non-Asian
patients.
Roy S. Herbst, MD, Ph.D., chief of Medical Oncology at Yale
Cancer Center and Smilow Cancer Hospital, New Haven, CT and
principal investigator in the Phase III ADAURA trial, said: "These
data are transformative for patients with early-stage EGFR-mutated
non-small cell lung cancer who face high rates of recurrence even
after successful surgery and subsequent treatment with adjuvant
chemotherapy. Tagrisso will provide a much-needed new treatment
option that has the potential to change the practice of medicine
and improve outcomes for patients in this setting."
José Baselga, Executive Vice President, Oncology R&D, said:
"The momentous results of the Phase III ADAURA trial for Tagrisso
demonstrate for the first time in a global trial that an EGFR
inhibitor can change the course of early-stage EGFR-mutated lung
cancer and provide hope for a cure. We are discussing these
outstanding data with regulatory authorities and look forward to
bringing the benefits of Tagrisso to patients with early-stage
disease."
In April 2020 , an Independent Data Monitoring Committee
recommended for the Phase III ADAURA trial to be unblinded two
years early based on its determination of overwhelming efficacy. At
the time of data cut-off, overall survival (OS) data favoured
Tagrisso, but were not mature. The trial will continue to assess OS
as a secondary endpoint.
Summary of ADAURA results
Tagrisso Placebo
DFS Stages II-IIIA (primary endpoint)(i) (n=233) (n=237)
--------------- ---------------
HR (95% CI) 0.17 (0.12, 0.23)
--------------------------------
p-value p<0.0001
--------------------------------
DFS rates (95% CI)
--------------- ---------------
One year 97% (94%, 99%) 61% (54%, 67%)
--------------- ---------------
Two years 90% (84%, 93%) 44% (37%, 51%)
--------------- ---------------
Three years 80% (68%, 88%) 28% (19%, 38%)
--------------- ---------------
DFS Stages IB-IIIA (secondary (n=339) (n=343)
endpoint)(i)
--------------- ---------------
HR (95% CI) 0.21 (0.16, 0.28)
--------------------------------
p-value p<0.0001
--------------------------------
DFS rates (95% CI)
--------------- ---------------
One year 97% (95%, 99%) 69% (63%, 73%)
--------------- ---------------
Two years 89% (84%, 92%) 53% (47%, 59%)
--------------- ---------------
Three years 79% (69%, 86%) 41% (33%, 49%)
--------------- ---------------
i The data cut-off date for DFS was 17 January 2020.
The safety and tolerability of Tagrisso in this trial was
consistent with previous trials in the metastatic setting. Adverse
events at Grade 3 or higher from all causes occurred in 10% of
patients in the Tagrisso arm versus 3% in the placebo arm as
assessed by the investigator.
Tagrisso is approved for the 1st-line treatment of patients with
locally advanced or metastatic EGFRm NSCLC in the US, Japan, China,
the EU and many other countries around the world.
Several presentations featured during the ASCO20 Virtual
Scientific Program will showcase AstraZeneca's leadership in lung
cancer across early and late-stage disease and reinforce the
Company's biomarker-driven approach.
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.(1)
Lung cancer is broadly split into NSCLC and small cell lung cancer,
with 80-85% classified as NSCLC.(2) A significant portion of
patients with resectable NSCLC eventually develop recurrence
despite surgery (complete resection).(3,4) Approximately 10-15% of
NSCLC patients in the US and Europe, and 30-40% of patients in Asia
have EGFRm NSCLC.(5-7) These patients are particularly sensitive to
treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block
the cell-signalling pathways that drive the growth of tumour
cells.(8) Approximately 25-30% of patients with NSCLC present with
resectable disease at diagnosis.(9-11)
ADAURA
ADAURA is a randomised, double-blinded, global,
placebo-controlled Phase III trial in the adjuvant treatment of 682
patients with Stage IB, II, IIIA EGFRm NSCLC with complete tumour
resection and adjuvant chemotherapy as indicated. In the
experimental arm, patients were treated with Tagrisso 80mg
once-daily oral tablets for three years or until disease
recurrence. The trial enrolled in more than 200 centres across more
than 20 countries, including the US, in Europe, South America, Asia
and the Middle East. The primary endpoint is DFS in Stage II and
IIIA patients and a key secondary endpoint is DFS in Stage IB, II
and IIIA patients. The data readout was originally anticipated in
2022. The trial will continue to assess OS as a secondary
endpoint.
Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible
EGFR-TKI with clinical activity against CNS metastases. Tagrisso
40mg and 80mg once-daily oral tablets have received approval in the
US, Japan, China, the EU and many countries around the world for
1st-line EGFRm advanced NSCLC. Tagrisso is also being developed in
the Stage III, unresectable setting (LAURA), in combination with
chemotherapy (FLAURA2) and in combination with potential new
medicines to address resistance to EGFR-TKIs (SAVANNAH,
ORCHARD).
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and
potential new medicines in late-stage development for the treatment
of different forms of lung cancer spanning different histologies,
several stages of disease, lines of therapy and modes of action.
AstraZeneca aims to address the unmet needs of patients with EGFRm
tumours as a genetic driver of disease, which occur in 10-15% of
NSCLC patients in the US and EU and 30-40% of NSCLC patients in
Asia, with the approved medicines Iressa (gefitinib) and Tagrisso,
and its ongoing Phase III trials LAURA, and FLAURA2.(5-7)
AstraZeneca is committed to addressing tumour mechanisms of
resistance through the ongoing Phase II trials SAVANNAH and ORCHARD
which test Tagrisso in combination with savolitinib, a selective
inhibitor of c-MET receptor tyrosine kinase, along with other
potential new medicines. Enhertu (trastuzumab deruxtecan), a
HER2-directed antibody drug conjugate is in development for
metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC
including trials in combination with other anticancer
treatments.
An extensive late-stage Immuno-Oncology programme focuses on
lung cancer patients without a targetable genetic mutation which
represents up to three-quarters of all patients with lung
cancer.(12) Imfinzi, an anti-PDL1 antibody, is in development for
patients with advanced disease (Phase III trials POSEIDON and
PEARL) and for patients in earlier stages of disease including
potentially curative settings (Phase III trials MERMAID-1, AEGEAN,
ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both
as monotherapy and in combination with tremelimumab and/or
chemotherapy. Imfinzi is also in development in the Phase II trials
NeoCOAST, COAST and HUDSON in combination with potential new
medicines from the early-stage pipeline including Enhertu .
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 six new
medicines launched between 2014 and 2020, and a broad pipeline of
small molecules and biologics in development, the Company is
committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and one day eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, 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 Twitter @ AstraZeneca .
Contacts
For details on how to contact the Investor Relations Team,
please click here . For Media contacts, click here .
References
1. World Health Organization. International Agency for Research
on Cancer. Globocan Worldwide Fact Sheet 2018. Available at
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Accessed:
May 2020.
2. LUNGevity Foundation. Types of Lung Cancer. Available at
https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer
Accessed: May 2020.
3. Sasaki H, et al. Prognosis of recurrent non--small cell lung
cancer following complete resection. Onc Letters.
2014:7;1300-1304.
4. Fink-Neuboeck N, et al. Hazards of Recurrence, Second
Primary, or Other Tumor at Ten Years After Surgery for
Non-Small-Cell Lung Cancer. Clinical Lung Cancer. February 25 2020.
https://doi.org/10.1016/j.cllc.2020.02.011.
5. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on
Cytological and Histological Samples in Non-Small Cell Lung Cancer:
a Polish, Single Institution Study and Systematic Review of
European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
6. 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.
7. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a
Review of Available Methods and Their Use for Analysis of Tumour
Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
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.
9. Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab Med.
2013;137:1191-1198.
10. Datta D, et al. Preoperative Evaluation of Patients
Undergoing Lung Resection Surgery. Chest. 2003;123: 2096-2103.
11. Le Chevalier T. Adjuvant chemotherapy for resectable
non-small-cell lung cancer: where is it going? Ann Oncol.
2010;21:196-8.
12. Pakkala, S, et al. Personalized Therapy for Lung Cancer:
Striking a Moving Target. JCI Insight. 2018;3(15):e120858.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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