Nearly three in four patients treated with
adjuvant TAGRISSO were alive and disease-free at four years
Exploratory results showed TAGRISSO also
reduced the risk of disease recurrence in the brain or spinal cord
by 76% in patients with Stage II-IIIA disease
Updated results from the pivotal ADAURA Phase III trial showed
that AstraZeneca’s TAGRISSO® (osimertinib) demonstrated a
sustained, clinically meaningful improvement in disease-free
survival (DFS) compared to placebo 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 tumor resection with curative intent.
These late-breaking results will be presented today at the
European Society for Medical Oncology (ESMO) Congress 2022 in Paris
(abstract #LBA47).
With an additional two years of follow-up from the 2020 readout,
allowing all patients the opportunity to complete three years of
adjuvant treatment, TAGRISSO reduced the risk of disease recurrence
or death by 77% (based on a hazard ratio [HR] of 0.23; 95%
confidence interval [CI] 0.18-0.30) in the primary analysis
population (Stages II-IIIA) and by 73% (HR 0.27; 95% CI 0.21-0.34)
in the overall trial population (Stages IB-IIIA). A median DFS of
nearly five and a half years (65.8 months) was seen in both the
primary and overall populations treated with TAGRISSO, compared to
21.9 and 28.1 months in the primary and overall populations,
respectively, treated with placebo.
While up to 30% of all patients with NSCLC may be diagnosed
early enough to have surgery with curative intent, recurrence is
still common in early-stage disease.1,2 Historically, approximately
half of patients diagnosed in Stages I-II, and three quarters of
patients diagnosed in Stage III, have experienced recurrence within
five years of resection.3,4
Results from an additional, prespecified exploratory analysis
showed TAGRISSO reduced the risk of central nervous system (CNS)
disease recurrence by 76% in patients with Stage II-IIIA disease
(HR: 0.24; 95% CI 0.14-0.42). At four years, 90% of patients in the
TAGRISSO arm were disease-free in the brain and spinal cord (95% CI
85-94%) compared to 75% of patients in the placebo arm (95% CI
67-81%). CNS disease recurrence refers to the spread of tumors to
the brain or spinal cord, a frequent complication of EGFRm NSCLC
associated with an especially poor prognosis.
Masahiro Tsuboi, MD, PhD, Chief and Director, Department of
Thoracic Surgery & Oncology, National Cancer Center Hospital
East, Japan, and principal investigator in the ADAURA trial, said:
“The updated ADAURA results show us that adjuvant osimertinib not
only continues to strikingly prolong the time patients with
early-stage EGFR-mutated lung cancer are living cancer-free after
surgery, but also continues to reduce the risk of tumors recurring
in the central nervous system over time. These results reinforce
adjuvant osimertinib as a standard-of-care treatment for these
early-stage lung cancer patients who previously had no targeted
treatment options after surgery, and who otherwise face high rates
of disease recurrence.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca said: “It is remarkable that just two years ago,
patients with early-stage EGFR-mutated lung cancer had no targeted
treatment options after surgery. Now, around the world, patients
have access to TAGRISSO and its added benefit of protecting the
brain and spinal cord. We look forward to mature overall survival
results for ADAURA in due time, but our research and commitment to
early-stage lung cancer patients continue through our broader
TAGRISSO program, which is investigating a prolonged duration of
post-surgery treatment and the potential role of adjuvant TAGRISSO
in even earlier stages of disease.”
Summary of efficacy resultsi:
TAGRISSO
Placebo
DFS Stages II-IIIA (primary
population)
(n=233)
(n=237)
HR (95% CI)
0.23 (0.18, 0.30)
Median DFS (months)
65.8 (54.4-NCii)
21.9 (16.6-27.5)
Landmark DFS rates (95% CI)
Two years
90% (85-93)
46% (40-52)
Three years
84% (78-88)
34% (28-40)
Four years
70% (62-76)
29% (23-35)
DFS Stages IB-IIIA (overall
population)
(n=339)
(n=343)
HR (95% CI)
0.27 (0.21, 0.34)
Median DFS (months)
65.8 (61.7-NC)
28.1 (22.1-35.0)
Landmark DFS rates (95% CI)
Two years
90% (86-93)
55% (49-60)
Three years
85% (80-88)
44% (39-50)
Four years
73% (67-78)
38% (32-43)
CNS DFS Stages II-IIIA
(n=22; 9%)
(n=41; 17%)
HR (95% CI)
0.24 (0.14, 0.42)
Landmark CNS DFS rates (95% CI)
Two years
98% (95-99)
81% (75-87)
Three years
97% (93-98)
77% (70-83)
Four years
90% (85-94)
75% (67-81)
Probability of CNS
recurrenceiii
Stages II-IIIA
(n=233)
(n=237)
Three years
2% (0.9-5)
13% (8.5-18.5)
i.
Data cut-off: April 11, 2022
ii.
NC: Not calculable
iii.
Defined as the probability of observing a
CNS recurrence event, conditional on the patient not experiencing a
competing risk event (non-CNS recurrence and death by any
cause)
The safety and tolerability of TAGRISSO in this trial were
consistent with its established profile. No new safety concerns
were reported with an extended treatment duration. Adverse events
at Grade 3 or higher from all causes occurred in 23% of patients in
the TAGRISSO arm versus 14% in the placebo arm.
IMPORTANT SAFETY INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of
the 1479 TAGRISSO-treated patients; 0.3% 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 1479 TAGRISSO-treated patients in
clinical trials, 0.8% were found to have a QTc >500 msec, and
3.1% 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 3% of the 1479 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 3.2% of 1233 patients who had baseline and
at least one follow-up LVEF assessment. In the ADAURA study, 1.5%
(5/325) of TAGRISSO-treated patients experienced LVEF decreases
≥10% from baseline and a drop to <50%. 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 1479 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
- Postmarketing cases of cutaneous vasculitis including
leukocytoclastic vasculitis, urticarial vasculitis, and IgA
vasculitis have been reported in patients receiving TAGRISSO.
Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate
for systemic involvement, and consider dermatology consultation. If
no other etiology can be identified, consider permanent
discontinuation of TAGRISSO based on severity
- 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 (≥20%) adverse reactions, including laboratory
abnormalities, were leukopenia, lymphopenia, thrombocytopenia,
diarrhea, anemia, rash, musculoskeletal pain, nail toxicity,
neutropenia, dry skin, stomatitis, fatigue, and cough
INDICATIONS
- TAGRISSO is indicated as adjuvant therapy after tumor resection
in adult patients with 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 first-line treatment of adult
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 adult 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
For additional information, please see the complete
Prescribing Information, including Patient Information.
You may report side effects related to AstraZeneca products by
clicking here.
CI, confidence interval; DFS, disease-free survival; EGFRm,
epidermal growth factor receptor mutation positive; HR, hazard
ratio; NE, not estimable; NSCLC, non-small cell lung cancer; OS,
overall survival; PFS, progression-free survival.
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.5
Lung cancer is broadly split into NSCLC and small cell lung cancer,
with 80-85% classified as NSCLC.6 The majority of all NSCLC
patients are diagnosed with advanced disease while approximately
25-30% present with resectable disease at diagnosis.1,2
Among patients with resectable tumors (Stage IB-IIIA), the
majority of patients eventually develop recurrence despite complete
tumor resection and adjuvant chemotherapy.3 In the absence of
organized screening efforts, early-stage lung cancer diagnoses are
often only made when the cancer is found on imaging for an
unrelated condition.7,8
Approximately 10-15% of NSCLC patients in the US and Europe, and
30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are
particularly sensitive to treatment with an EGFR-tyrosine kinase
inhibitor (EGFR-TKI) which block the cell-signaling pathways that
drive the growth of tumor cells.12
ADAURA
ADAURA is a randomized, double-blind, placebo-controlled, global
Phase III trial in the adjuvant treatment of 682 patients with
Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection
and, at physicians’ and patients’ discretion, adjuvant
chemotherapy. Patients were treated with TAGRISSO 80mg once-daily
oral tablets or placebo 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 was DFS in Stage II and IIIA
patients and a key secondary endpoint was DFS in Stage IB, II and
IIIA patients.
Though the primary data readout was originally anticipated in
2022, data from the trial were first reported early in 2020,
following a recommendation from an Independent Data Monitoring
Committee (IDMC) based on its determination of overwhelming
efficacy. 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
central nervous system metastases. TAGRISSO (40mg and 80mg
once-daily oral tablets) has been used to treat approximately
575,000 patients across indications worldwide and AstraZeneca
continues to explore TAGRISSO as a treatment for patients across
multiple stages of EGFRm NSCLC.
In Phase III trials, TAGRISSO is being investigated in the
neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3
adjuvant resectable setting (ADAURA2), in the Stage III locally
advanced unresectable setting following chemoradiation therapy
(LAURA), and in combination with chemotherapy in the advanced
setting (FLAURA2). AstraZeneca is also researching ways to address
tumor mechanisms of resistance through the SAVANNAH and ORCHARD
Phase II trials, and the SAFFRON Phase III trial, which test
TAGRISSO given concomitantly with 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
osimertinib; durvalumab and tremelimumab; fam-trastuzumab
deruxtecan-nxki and datopotamab deruxtecan in collaboration with
Daiichi Sankyo; 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 catalyze 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.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development, and commercialization
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. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References
- Le Chevalier T. Adjuvant Chemotherapy for Resectable
Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol.
2010;21:196-8.
- Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. ArchivesPathology Lab Med.
2013;137:1191-1198.
- Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin Oncol.
2008;26:3552-3559.
- Peters, S. Lungscape: resected non-small-cell lung cancer
outcome by clinical and pathological parameters. Thorac Oncol.
2014;9(11):1675-84.
- World Health Organisation. International Agency for Research on
Cancer. All Cancers Fact Sheet. Available at
https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf.
Accessed August 2022.
- American Cancer Society. What Is Lung Cancer? Available at:
https://www.cancer.org/cancer/lung-cancer/about/what-is.html.
Accessed August 2022.
- Sethi S, et al. Incidental Nodule Management – Should There Be
a Formal Process? Journal of Thorac Onc. 2016:8;S494-S497.
- LUNGevity Foundation. Screening and Early Detection. Available
at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection.
Accessed August 2022.
- 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.
- 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.
- 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.
- 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.
US-68403 Last Updated
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Brendan McEvoy, +1 302 885 2677 Jessica McDuell, +1 302 885
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