Results from an exploratory analysis of the ADAURA phase III trial have shown Osimertinib ( Tagrisso ) has extended disease-free survival ( DFS ) in patients with epidermal growth factor receptor-mutated ( EGFRm ) non-small cell lung cancer ( NSCLC ) regardless of prior adjuvant chemotherapy treatment or stage of disease.
Osimertinib is a third-generation, irreversible EGFR-TKI with clinical activity against CNS metastases.
In this exploratory analysis of the overall trial population, adjuvant Osimertinib has reduced the risk of disease recurrence or death by 84% in patients who had been treated with prior adjuvant chemotherapy ( based on a hazard ratio [ HR ] of 0.16, 95% confidence interval [ CI ] 0.10-0.26 ) and by 77% in patients who had not ( HR 0.23; 95% CI 0.13-0.40 ).
Disease-free survival benefits were similar across each stage of disease.
In addition, a separate exploratory post-hoc analysis of patient-reported outcomes in ADAURA has shown that patients treated with Osimertinib maintained their quality of life, with no clinically meaningful differences in physical or mental health measures in the Osimertinib and placebo arms.
In the ADAURA trial, chemotherapy use was balanced across the two treatment arms, with 60% of patients receiving prior adjuvant chemotherapy.
In line with uptake observed in prior studies and clinical practice, younger patients ( less than 70 years ) and those with more advanced disease were more likely to have prior adjuvant chemotherapy.
Treatment with chemotherapy did not vary according to a patient’s performance status.
The safety and tolerability of Osimertinib was consistent with previous trials in the metastatic EGFRm NSCLC setting.
Adverse events at grade 3 or higher from all causes occurred in 20% of patients in the Osimertinib arm versus 13% in the placebo arm as assessed by investigators.
Primary results of ADAURA, which were published in The New England Journal of Medicine in September 2020, showed adjuvant treatment with Osimertinib reduced the risk of disease recurrence or death by 83% ( HR=0.17; 95% CI 0.12-0.23; p less than 0.0001 ) among patients with stage II and IIIA EGFRm NSCLC and, as shown in a prespecified exploratory analysis, demonstrated a clinically meaningful improvement in central nervous system ( CNS ) disease-free survival compared to placebo.
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.
Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.
The majority of all 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 NSCLC. These patients are particularly sensitive to treatment with an EGFR-TKI which blocks the cell-signalling pathways that drive the growth of tumour cells. ( Xagena )
Source: AstraZeneca, 2021