AstraZeneca PLC - Tagrisso reduced early lung cancer brain recurrenc
Tagrisso reduced the risk of disease recurrence in the brain by 82%
in the adjuvant treatment of early-stage EGFR-mutated lung cancer
ADAURA Phase III trial data at ESMO reinforce the proven clinical
activity of Tagrisso in treating central nervous system metastases
Results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca's Tagrisso (osimertinib) demonstrated a clinically meaningful improvement in central nervous system (CNS) 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.
While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease.1-3 CNS recurrence, when cancer spreads to the brain, is a frequent complication of EGFRm NSCLC and these patients have an especially poor prognosis.4-5
Results were presented on
This analysis showed that fewer patients treated with Tagrisso in the adjuvant setting had recurrence events or deaths compared to placebo (11% versus 46%). Among patients whose cancer recurred, 38% of those treated with Tagrisso had a metastatic recurrence compared to 61% of patients on placebo. Tagrisso showed an 82% reduction in the risk of CNS recurrence or death (based on a hazard ratio [HR] of 0.18; 95% confidence interval [CI] 0.10-0.33; p<0.0001). Median CNS DFS was not yet reached in either arm.
In a post-hoc analysis, the estimated probability of observing disease recurrence in the brain at 18 months for patients treated with Tagrisso was less than 1% versus 9% for placebo among patients who had not experienced another type of recurrence. On the primary endpoint of DFS in patients with Stage II and IIIA disease, Tagrisso in the adjuvant setting reduced the risk of disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23; p<0.0001).
Summary of exploratory results on CNS recurrence in the ADAURA Phase III trial
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HR (95% CI)
CNS DFS events, patients (%):
DFS events, patients (%):
Type of disease recurrence
i. Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.
ii. Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.
The safety and tolerability of Tagrisso in this trial was consistent with previous trials in the metastatic EGFRm NSCLC 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 investigators.
Tagrisso is not currently approved in the adjuvant setting in any country. Tagrisso received Breakthrough Therapy Designation in
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.7 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3
For those with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.8 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.9-10
Approximately 10-15% of NSCLC patients in the US and
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 following complete tumour resection and adjuvant chemotherapy as indicated. 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 centres across more than 20 countries, including the US, in
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. Tagrisso 40mg and 80mg once-daily oral tablets have received approval in the US,
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 with the approved medicines Iressa (gefitinib) and Tagrisso and its ongoing Phase III trials LAURA, NeoADAURA and FLAURA2.
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.
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 seven 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.
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 (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
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