Osimertinib in UntreatedEGFR-Mutated Advanced Non–Small-Cell Lung Cancer Academic Article uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • BACKGROUND: 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). METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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 .).


  • Juergens, Rosalyn
  • Soria, Jean-Charles
  • Ohe, Yuichiro
  • Vansteenkiste, Johan
  • Reungwetwattana, Thanyanan
  • Chewaskulyong, Busyamas
  • Lee, Ki Hyeong
  • Dechaphunkul, Arunee
  • Imamura, Fumio
  • Nogami, Naoyuki
  • Kurata, Takayasu
  • Okamoto, Isamu
  • Zhou, Caicun
  • Cho, Byoung Chul
  • Cheng, Ying
  • Cho, Eun Kyung
  • Voon, Pei Jye
  • Planchard, David
  • Su, Wu-Chou
  • Gray, Jhanelle E
  • Lee, Siow-Ming
  • Hodge, Rachel
  • Marotti, Marcelo
  • Rukazenkov, Yuri
  • Ramalingam, Suresh S

publication date

  • January 11, 2018

has subject area