Tagrisso ( Osimertinib ), an irreversible epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR TKI ), has been approved in the European Union ( EU ) for the adjuvant treatment of adult 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.
Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 ( L858R ) mutations.
The approval by the European Commission was based on positive results from the ADAURA phase III trial in which Osimertinib has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival ( DFS ) in the primary analysis population of patients with stage II and IIIA EGFRm NSCLC.
The trial has also showed a statistically significant and clinically meaningful improvement in DFS for Osimertinib in the overall trial population, a key secondary endpoint.
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.
Historically, nearly half of patients diagnosed in stage IB, and over three quarters of patients diagnosed in stage IIIA, have experienced disease recurrence within five years.
About a fifth of the world’s lung cancer patients are in the EU and among those with NSCLC, approximately 15% have tumours with an EGFR mutation.
In the ADAURA trial, adjuvant treatment with Osimertinib has reduced the risk of disease recurrence or death by 83% in patients with stage II and IIIA disease ( hazard ratio [ HR ] 0.17; 99.06% confidence interval [ CI ] 0.11-0.26; p less than 0.001 ) and by 80% in the overall trial population of patients with stage IB-IIIA disease ( hazard ratio, HR=0.20; 99.12% CI 0.14-0.30; p less than 0.001 ).
Consistent DFS results were seen regardless of prior adjuvant chemotherapy use and across all prespecified subgroups.
The safety and tolerability of Osimertinib in this trial was consistent with previous trials in the metastatic setting.
The ADAURA results were published in The New England Journal of Medicine ( NEJM ).
ADAURA is a randomised, double-blind, global, placebo-controlled phase III trial in the adjuvant treatment of 682 patients with stage IB, II and IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy.
Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.
The trial enrolled patients 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 was disease-free survival in stage II and IIIA patients and a key secondary endpoint was disease-free survival in stage IB, II and IIIA patients.
The data readout was originally anticipated in 2022. In April 2020, an Independent Data Monitoring Committee recommended for the trial to be unblinded two years early based on a determination of overwhelming efficacy.
The trial will continue to assess overall survival.
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.
Lung cancer is broadly split into non-small cell lung cancer and small cell lung cancer, with 80-85% classified as NSCLC.
The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.
Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.
For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.
Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm non-small cell lung cancer. These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor which blocks the cell-signalling pathways that drive the growth of tumour cells. ( Xagena )
Source: AstraZeneca, 2021