EGFR mutations are seen in about 15-35% of patients with lung adenocarcinoma which is by far the most common histological subtype. For patients with EGFR mutation EGFR inhibition is the standard of care at this point and the approved agents are gefitinib, erlotinib and afatinib. What we are reporting today is new data comparing osimertinib, which is a third generation EGFR inhibitor, comparing it to the current standard of care. Osimertinib has many advantages – it’s a very highly specific inhibitor of the mutated receptor compared to wildtype receptor. It also inhibits the T790 pathway which is a common resistance mechanism for cells exposed to EGFR tyrosine kinase inhibitors and it’s also better tolerated relative to the other EGFR inhibitors. So for all these reasons we compared osimertinib to the standard of care in the FLAURA study.
Can you tell us about the design of the FLAURA study?
The FLAURA study was a double blind, placebo controlled randomised trial. 556 patients were enrolled and randomised 1:1 to receive either osimertinib at a dose of 80mg/day or erlotinib or gefitinib at their standard doses. The primary endpoint was progression free survival and the secondary endpoints included response rate, duration of response, safety and overall survival.
Patients in the control group were allowed to cross over and receive osimertinib if they had documented progression and developed a T790M mutation and in fact many patients did that.
Can you tell us about the results?
The progression free survival was clearly superior for patients who received osimertinib. The median PFS was improved from 10.2 months in the control group to 18.9 months with osimertinib with a hazard ratio of 0.46 and a highly significant p-value. So, in other words, there was a 54% reduction in the risk of progression or death for patients treated with osimertinib. We also found that the activity in the brain was robust, the hazard ratio for patients who had brain metastases coming into the study was very similar to that of patients who did not have brain metastases coming in. So osimertinib exerted an effect in both systemic sites and the brain. The median duration of response was more than doubled with osimertinib; for the control group it was 8.5 months, for osimertinib it was 17.2 months. So all efficacy parameters favoured osimertinib. Finally, overall survival – while the results are immature, only 25% of maturity has been achieved, the hazard ratio was 0.63 favouring osimertinib. These are very promising survival trends and for all these reasons we feel that the FLAURA study clearly establishes osimertinib as a new standard of care for patients with exon 19 or 21 mutation in the first line setting.
The overall survival reports that we are presenting today factor in the fact that a subset of patients have crossed over.
Is this practice ready?
It is our hope that these data will be reviewed favourably by the agencies and the drug would be available for first line use in the near future.