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Clinical Trial
. 2018 Jan 11;378(2):113-125.
doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

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

Jean-Charles Soria  1 , Yuichiro Ohe  1 , Johan Vansteenkiste  1 , Thanyanan Reungwetwattana  1 , Busyamas Chewaskulyong  1 , Ki Hyeong Lee  1 , Arunee Dechaphunkul  1 , Fumio Imamura  1 , Naoyuki Nogami  1 , Takayasu Kurata  1 , Isamu Okamoto  1 , Caicun Zhou  1 , Byoung Chul Cho  1 , Ying Cheng  1 , Eun Kyung Cho  1 , Pei Jye Voon  1 , David Planchard  1 , Wu-Chou Su  1 , Jhanelle E Gray  1 , Siow-Ming Lee  1 , Rachel Hodge  1 , Marcelo Marotti  1 , Yuri Rukazenkov  1 , Suresh S Ramalingam  1 ; FLAURA Investigators
Collaborators, Affiliations
Free article
Clinical Trial

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

Jean-Charles Soria et al. N Engl J Med. .
Free article

Abstract

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 .).

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