July 22, 2024

Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation–positive advanced non–small-cell lung cancer (NSCLC).


In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation–positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily).

The primary end point was investigator-assessed progression-free survival.


The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18. 9 months vs. 10. 2 months; hazard ratio for disease progression or death, 0. 46; 95% confidence interval CI, 0. 37 to 0. 57; P<0. 001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1. 27; 95% CI, 0. 85 to 1. 90; P=0. 24).

The median duration of response was 17. 2 months (95% CI, 13. 8 to 22. 0) with osimertinib versus 8. 5 months (95% CI, 7. 3 to 9. 8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0. 63; 95% CI, 0. 45 to 0. 88; P=0. 007 nonsignificant in the interim analysis). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).


Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation–positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials. gov number, NCT02296125. )

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