Yi-Long Wu, et al.

Background: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR)mutation-positive advanced non-small-cell lung cancer (NSCLC).The efficacy and safety of osimertinib as adjuvant therapy are unknown.

Methods: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years.The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment).The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety.

Results: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group).At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93)and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001).In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months(overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001).At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33).Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group).No new safety concerns were noted.

Conclusions: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo.(Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).