First Phase III trial to demonstrate
survival benefit in this adjuvant setting
Positive high-level results from the ADAURA Phase III trial
showed AstraZeneca’s TAGRISSO® (osimertinib) demonstrated a
statistically significant and clinically meaningful improvement in
overall survival (OS), a key secondary endpoint, 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.
In May 2020, AstraZeneca announced TAGRISSO demonstrated a
statistically significant and clinically meaningful improvement in
disease-free survival (DFS) in this setting. In September 2022,
updated results demonstrated a median DFS of nearly five and a half
years.
Per the ADAURA trial protocol, patients on placebo that recurred
with metastatic disease had the opportunity to receive open-label
TAGRISSO.
Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical
Oncology at Yale Cancer Center and Smilow Cancer Hospital, New
Haven, Connecticut, and principal investigator in the ADAURA Phase
III trial, said: “These new survival data for osimertinib reinforce
the unprecedented ADAURA disease-free survival results and confirm
its potential to extend patients’ lives in early-stage disease. The
ADAURA results provide powerful evidence that osimertinib offers
the best possible care for patients with early-stage EGFR-mutated
non-small cell lung cancer who historically faced high rates of
recurrence and previously had no targeted options after
surgery.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The ADAURA trial brought the first targeted
medicine to patients with early-stage EGFR-mutated non-small cell
lung cancer. Today, these exciting overall survival results
validate adjuvant TAGRISSO as the standard of care in this setting
and reinforce the importance of early diagnosis and testing for
EGFR mutation in lung cancer.”
The safety and tolerability of TAGRISSO in the ADAURA trial were
consistent with its established profile and no new safety concerns
were reported.
These new ADAURA OS results in the early-stage resectable
setting add to the extensive body of evidence for TAGRISSO in EGFRm
NSCLC which has now shown a statistically significant and
clinically meaningful OS benefit in both the early adjuvant and
late-stage metastatic settings. The data will be presented at a
forthcoming medical meeting.
Each year there are an estimated 2.2 million people diagnosed
with lung cancer globally with 80-85% of patients diagnosed with
NSCLC, the most common form of lung cancer.1-3 Approximately 25-30%
of all patients with NSCLC are diagnosed early enough to have
surgery with curative intent.4‑5 Further, 73% of patients with
Stage IB and 56-65% of patients with Stage II disease will survive
for five years.6 This decreases to 41% for patients with Stage IIIA
and 24% for patients with Stage IIIB disease, reflecting a high
unmet medical need.6
AstraZeneca has several ongoing registrational trials focused on
testing TAGRISSO in earlier stages of lung cancer, including in the
neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3
adjuvant resectable setting (ADAURA2), and in the Stage III locally
advanced unresectable setting (LAURA).
TAGRISSO is approved to treat early-stage lung cancer in more
than 90 countries, including in the US, EU, China and Japan, and
additional global regulatory reviews are ongoing. TAGRISSO is also
approved for the 1st-line treatment of patients with locally
advanced or metastatic EGFRm NSCLC and for the treatment of locally
advanced or metastatic EGFR T790M mutation-positive NSCLC in the
US, EU, China, Japan and many other countries.
AstraZeneca has a comprehensive portfolio of approved and
potential new medicines in development for patients with lung
cancer. In addition to these results, the Company has also
announced today positive results from the AEGEAN Phase III trial of
durvalumab in combination with neoadjuvant chemotherapy before
surgery and as adjuvant monotherapy after surgery in Stage IIA-IIIB
resectable NSCLC.
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 occurs 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
- Aplastic anemia has been reported in patients treated with
TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some
cases had a fatal outcome. Inform patients of the signs and
symptoms of aplastic anemia including but not limited to, new or
persistent fevers, bruising, bleeding, and pallor. If aplastic
anemia is suspected, withhold TAGRISSO and obtain a hematology
consultation. If aplastic anemia is confirmed, permanently
discontinue TAGRISSO. Perform complete blood count with
differential before starting TAGRISSO, periodically throughout
treatment, and more frequently if indicated
- 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
Please see complete Prescribing Information, including Patient
Information for TAGRISSO.
You may report side effects related to AstraZeneca products by
clicking here.
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.1
Lung cancer is broadly split into NSCLC and small cell lung
cancer.2 The majority of all NSCLC patients are diagnosed with
advanced disease while approximately 25-30% present with resectable
disease at diagnosis.4‑5 Early-stage lung cancer diagnoses are
often only made when the cancer is found on imaging for an
unrelated condition.7‑8
For patients with resectable tumors, the majority eventually
develop recurrence despite complete tumor resection and adjuvant
chemotherapy.9
ADAURA
ADAURA was 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 was enrolled in more than 200 centers across more than
20 countries, including the US, Europe, South America, Asia and the
Middle East. The primary endpoint was DFS in Stage II and IIIA
patients and key secondary endpoints included DFS in Stage IB, II
and IIIA patients, and OS in both the primary and overall
populations.
Though the primary data readout was originally anticipated in
2022, data from the trial were reported early following a
recommendation from an Independent Data Monitoring Committee (IDMC)
based on its determination of overwhelming efficacy.
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 nearly
700,000 patients across its indications worldwide and AstraZeneca
continues to explore TAGRISSO as a treatment for patients across
multiple stages of EGFRm NSCLC.
In addition to investigating TAGRISSO in early-stage disease,
AstraZeneca is also studying the medicine in combination with
chemotherapy in locally advanced and metastatic EGFRm NSCLC
(FLAURA2). The Company 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
tremelimumab and gefitinib; 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.
AstraZeneca
AstraZeneca 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-us.com and follow the Company on
Twitter @AstraZenecaUS.
References
- 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 March 2023.
- LUNGevity Foundation. Types of Lung Cancer. Available at
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed March 2023.
- Cheema PK, et al. Perspectives on treatment advances for stage
III locally advanced unresectable non-small-cell lung cancer. Curr
Oncol. 2019;26(1):37-42.
- Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab Med.
2013;137:1191-1198.
- Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable
Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol.
2010;21:vii196-vii198.
- Goldstraw P, et al. The IASLC Lung Cancer Staging Project:
Proposals for Revision of the TNM Stage Groupings in the
Forthcoming (Eighth) Edition of the TNM Classification for Lung
Cancer. J Thorac Oncol. 2016;11(1):39-51.
- Sethi S, et al. Incidental Nodule Management – Should There Be
a Formal Process? J Thorac Oncol. 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 March 2023.
- Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin Oncol.
2008;26:3552-3559.
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