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 (Stage IB, II and IIIA) epidermal growth factor
receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after
complete tumor resection with curative intent.
Results will be presented during the plenary session of the
American Society of Clinical Oncology ASCO20 Virtual Scientific
Program on May 31, 2020 (abstract #LBA5).
In the primary endpoint of DFS in patients with Stage II and
IIIA disease, adjuvant (after surgery) treatment 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 all 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 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, PhD, 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 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 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
endpoint)i
(n=339)
(n=343)
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%)
iThe data cut-off date for DFS was January 17, 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.
TAGRISSO IMPORTANT SAFETY INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of
the 1142 TAGRISSO-treated patients; 0.4% of cases were fatal.
Withhold TAGRISSO and promptly investigate for ILD in patients who
present with worsening of respiratory symptoms which may be
indicative of ILD (eg, 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 1142 TAGRISSO-treated patients in
clinical trials, 0.9% were found to have a QTc >500 msec, and
3.6% 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 2.6% of the 1142 TAGRISSO-treated
patients; 0.1% of cardiomyopathy cases were fatal. A decline in
left ventricular ejection fraction (LVEF) ≥10% from baseline and to
<50% LVEF occurred in 3.9% of 908 patients who had baseline and
at least one follow-up LVEF assessment. Conduct cardiac monitoring,
including 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, permanently discontinue
TAGRISSO
- Keratitis was reported in 0.7% of 1142 patients treated with
TAGRISSO 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
- Postmarketing cases consistent with Stevens-Johnson syndrome
(SJS) and erythema multiforme major (EMM) have been reported in
patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is
suspected and permanently discontinue if confirmed
- Verify pregnancy status of females of reproductive potential
prior to initiating TAGRISSO. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with TAGRISSO 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
- Most common adverse reactions (≥20%) were diarrhea, rash, dry
skin, nail toxicity, stomatitis, fatigue and decreased
appetite
INDICATIONS
- TAGRISSO is indicated for the first-line treatment of patients
with metastatic non-small cell lung cancer (NSCLC) whose tumors
have epidermal growth factor receptor (EGFR) exon 19 deletions or
exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated 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 EGFR
tyrosine kinase inhibitor (TKI) therapy
Please see complete Prescribing Information, including
Patient Information.
NOTES TO EDITORS
About 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-signaling pathways that drive the growth of tumor cells.8
Approximately 25-30% of patients with NSCLC present with resectable
disease at diagnosis.9-11
About ADAURA
ADAURA is a randomized, double-blinded, global,
placebo-controlled Phase III trial in the adjuvant treatment of 682
patients with Stage IB, II, and IIIA EGFRm NSCLC with complete
tumor resection and adjuvant chemotherapy as an option. In the
experimental arm, patients were treated with TAGRISSO 80 mg
once-daily oral tablets for three years or until disease
recurrence. The trial enrolled in more than 200 centers 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.
About TAGRISSO
TAGRISSO® (osimertinib) is a third-generation, irreversible
EGFR-TKI with clinical activity against CNS metastases. TAGRISSO 40
mg and 80 mg 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
tumors 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 gefitinib and TAGRISSO, and its
ongoing Phase III trials LAURA and FLAURA2.5-7
AstraZeneca is committed to addressing tumor 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. 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 program focuses on
lung cancer patients without a targetable genetic mutation which
represents up to three-quarters of all patients with lung cancer.12
Durvalumab, 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. Durvalumab 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 trastuzumab
deruxtecan.
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 focusing 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 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, Renal &
Metabolism, and Respiratory & Immunology. AstraZeneca operates
in over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please visit www.astrazeneca-us.com
and follow the Company on Twitter @AstraZenecaUS.
REFERENCES
1. World Health Organization. International Agency for Research
on Cancer. Globocan Worldwide Fact Sheet 2018.
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessed: May 2020.
2. LUNGevity Foundation. Types of Lung Cancer.
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 Lett.
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. Clin Lung Cancer.
2020:26;S1525-7304(20)30036-X.
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 PT, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Arch Pathol 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.
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