Osimertinib has been approved by the FDA, based on the results of the ADAURA trial, for adult patients who have early-stage non-small cell lung carcinoma (NSCLC) with EGFR-mutations.1 These mutations occur in about 10% of NSLCL patients. Treatment with osimertinib proved to be very effective in the trial, thus blinding was ended prematurely to ensure faster data publication. In Belgium, osimertinib is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR-mutations.2 After assessment by EMA, this indication could possibly be extended to NSCLC patients in an early stage of their disease.
The double-blind phase III-study ADAURA included 683 patients with EGFR-mutation-positive and completely resected NSCLC. The patients were randomised 1:1 to placebo (n=343) or osimertinib (n=339, 80 mg daily) and received this treatment for 3 years.3 The number of patients with stage 2 of 3a illness that was alive and disease-free after 2 year was twice as high when using osimertinib compared to placebo. The disease-free survival was 90% (95% CI: 84-93) with osimertinib and 44% (95% CI: 37-51) with placebo. This resulted in a hazard ratio (HR) of 0,17 (99% CI: 0,11-0,26; p<0,001).
The disease-free survival was 89% (95% CI: 95-99) in all analysed NSCLC patients that were treated with osimertinib for two years. Patients that received a placebo survived a lot less often without disease development; only 52% (95% CI: 46-58) did. This results in a HR of 0,20 (99% CI: 0,14-0,30; p<0,001). Moreover, the percentage of patients that was alive and did not develop a disease of the central nervous system was 98% with osimertinib and 85% with placebo (HR: 0,18; 95% CI: 0,10-0,33).
Overall survival was not reached yet, but 29 patients passed away during the analysed period, of which 9 received osimertinib and 20 placebo. The safety profile was similar to previous studies.
The disease-free survival was doubled in the ADAURA trial when early-stage (stage 1b to 3a) NSCLC patients with EGFR-mutations were treated with osimertinib instead of placebo. The FDA advised the expansion of the indication of osimertinib to include NSCLC patients in an early phase of their disease, based on these data. Osimertinib has not been approved by the EMA yet for this patient group but is currently going through expedited assessment.