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

 Jean-Charles Soria  ;  Yuichiro Ohe  ;  Johan Vansteenkiste  ;  Thanyanan Reungwetwattana  ;  Busyamas Chewaskulyong  ;  Ki Hyeong Lee  ;  Arunee Dechaphunkul  ;  Fumio Imamura  ;  Naoyuki Nogami  ;  Takayasu Kurata  ;  Isamu Okamoto  ;  Caicun Zhou  ;  Byoung Chul Cho  ;  Ying Cheng  ;  Eun Kyung Cho  ;  Pei Jye Voon  ;  David Planchard  ;  Wu-Chou Su  ;  Jhanelle E. Gray  ;  Siow-Ming Lee  ;  Rachel Hodge  ;  Marcelo Marotti  ;  Yuri Rukazenkov  ;  Suresh S. Ramalingam  ;  FLAURA Investigators 
 NEW ENGLAND JOURNAL OF MEDICINE, Vol.378(2) : 113-125, 2018 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/mortality ; Disease-Free Survival ; Double-Blind Method ; ErbB Receptors/genetics* ; Erlotinib Hydrochloride/therapeutic use ; Female ; Gefitinib ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Mutation* ; Piperazines/adverse effects ; Piperazines/therapeutic use* ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use* ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Quinazolines/therapeutic use ; Survival Rate
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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