Phase III FLAURA trial demonstrates 52% risk reduction of CNS disease progression or death in patients treated with Tagrisso (osimertinib) compared to current standard-of-care EGFR-TKIs*

CAMBRIDGE, England--(BUSINESS WIRE)--AstraZeneca today presented new data from a subgroup analysis of the Phase III FLAURA trial, which explored osimertinib as 1st-line therapy in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Results presented at the ESMO Asia 2017 Congress in Singapore showed that patients with central nervous system (CNS) metastases at baseline had a higher objective response rate with their brain metastasis and suggest a lower risk of CNS progression when treated with osimertinib, a third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI), versus current standard-of-care EGFR-TKIs (erlotinib or gefitinib) [Abstract LBA5].1

The analysis included patients with ≥1 measurable and/or non-measurable CNS lesion present on baseline scan (as assessed by blinded independent central review), accounting for 23% of the total FLAURA patient population (128 of 556 patients; 61 patients enrolled in the osimertinib arm and 67 patients in the comparator arm).1 In this pre-specified subgroup analysis, osimertinib demonstrated a nominally statistically significant improvement in CNS progression-free survival (PFS) compared with current standard of care, reducing the risk of CNS disease progression or death by more than half (hazard ratio 0.48; 95% confidence interval [CI] 0.26-0.86; nominal p=0.014).1 In addition, fewer patients in the osimertinib arm experienced disease progression due to the development of new CNS lesions, compared with patients in the comparator arm (12% vs. 30%).1 The CNS objective response rate (a measurement of tumour shrinkage) was also higher in patients treated with osimertinib at 66% vs. 43% for patients in the comparator arm (odds ratio 2.5; 95% CI 1.2, 5.2; p=0.011).1

The FLAURA safety data for osimertinib were in line with those observed in prior clinical trials.1,2Osimertinib was well tolerated, with less frequent Grade 3 or higher adverse events (AEs) than with standard EGFR-TKIs (34% vs. 45%). In patients treated with osimertinib, the most common AEs were diarrhoea (58% [2% Grade ≥3]) and dry skin (32% [<1% Grade ≥3]), and in the comparator arm group, the most common AEs were diarrhoea (57% [3% Grade ≥3]) and dermatitis acneiform (48% [5% Grade ≥3]).2

Dr. Johan Vansteenkiste, Respiratory Oncologist at the University Hospital KU Leuven, Leuven, Belgium, said: “CNS metastases, including brain metastases, are a common and very disabling complication of advanced EGFR mutation-positive NSCLC. They are notoriously difficult to treat, as existing oral therapies are often unable to effectively cross the blood-brain barrier. The CNS efficacy results for osimertinib in the FLAURA trial suggest improved clinical outcomes in an area of great unmet medical need.”

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Osimertinib represents the next generation of targeted therapies in EGFR mutation-positive NSCLC, and its CNS activity has been demonstrated in the AURA3, BLOOM and FLAURA trials. This subgroup analysis of FLAURA further supports data presented earlier this year in demonstrating the consistent benefit of osimertinib when used as a 1st-line therapy, irrespective of the presence of CNS metastases at study entry.”

Full results of the FLAURA trial were published online today in the New England Journal of Medicine(NEJM).