Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC)
with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment
for resected EGFR-mutated NSCLC. EGFR tyrosine kinase inhibitors have shown preliminary
efficacy in unresectable stage III EGFR-mutated NSCLC.In this phase 3, double-blind,
placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated
stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib
or placebo until disease progression occurred (as assessed by blinded independent
central review) or the regimen was discontinued. The primary end point was progression-free
survival as assessed by blinded independent central review.A total of 216 patients
who had undergone chemoradiotherapy were randomly assigned to receive osimertinib
(143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free
survival benefit as compared with placebo: the median progression-free survival was
39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for
disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24;
P<0.001). The percentage of patients who were alive and progression free at 12 months
was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo.
Interim overall survival data (maturity, 20%) showed 36-month overall survival among
84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI,
57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53).
The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group
and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported
in 48% and 38%, respectively. No new safety concerns emerged.Treatment with osimertinib
resulted in significantly longer progression-free survival than placebo in patients
with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov
number, NCT03521154.).
