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

被引:3824
|
作者
Soria, J. -C. [1 ,2 ]
Ohe, Y. [3 ]
Vansteenkiste, J. [8 ]
Reungwetwattana, T. [9 ]
Chewaskulyong, B. [10 ]
Lee, K. H. [12 ]
Dechaphunkul, A. [11 ]
Imamura, F. [4 ]
Nogami, N. [6 ]
Kurata, T. [5 ]
Okamoto, I. [7 ]
Zhou, C. [15 ]
Cho, B. C. [13 ]
Cheng, Y. [16 ]
Cho, E. K. [14 ]
Voon, P. J. [17 ]
Planchard, D. [1 ,2 ]
Su, W. -C. [18 ]
Gray, J. E. [19 ]
Lee, S. -M. [20 ,21 ]
Hodge, R. [22 ]
Marotti, M. [22 ]
Rukazenkov, Y. [22 ]
Ramalingam, S. S. [23 ]
Boyer, Michael
Lee, Chee
Hughes, Brett
O'Byrne, Kenneth
Briggs, Peter
Milward, Michael
John, Thomas
Demedts, Ingel
Vansteenkiste, Johan
Bustin, Frederique
Barrios, Carlos Henrique
Timcheva, Constanta
Butts, Charles
Goss, Glenwood
Juergens, Rosalyn
Leighl, Natasha
Cheng, Susanna
Burkes, Ronald
Zhou, Caicun
Zhang, Helong
Shu, Yongqian
Cheng, Ying
Zhou, Qing
Li, Wei
Feng, Guosheng
He, Yong
机构
[1] Gustave Roussy Canc Campus, Orsay, France
[2] Univ Paris Sud, Orsay, France
[3] Natl Canc Ctr, Dept Thorac Oncol, Tokyo, Japan
[4] Kansai Med Univ Hosp, Dept Thorac Oncol, Osaka Int Canc Inst, Osaka, Japan
[5] Kansai Med Univ Hosp, Dept Thorac Oncol, Osaka, Japan
[6] Natl Hosp Org, Shikoku Canc Ctr, Dept Thorac Oncol, Matsuyama, Ehime, Japan
[7] Kyushu Univ, Grad Sch Med Sci, Res Inst Dis Chest, Fukuoka, Japan
[8] Katholieke Univ Leuven, Univ Hosp, Resp Oncol Unit, Leuven, Belgium
[9] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok, Thailand
[10] Chiang Mai Univ, Dept Med, Oncol Unit, Chiang Mai, Thailand
[11] Prince Songkla Univ, Div Med Oncol, Dept Internal Med, Fac Med, Hat Yai, Thailand
[12] Chungbuk Natl Univ, Coll Med, Chungbuk Natl Univ Hosp, Div Med Oncol, Cheongju, South Korea
[13] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Dept Internal Med,Div Med Oncol, Seoul, South Korea
[14] Gachon Univ, Gil Med Ctr, Dept Internal Med, Div Hematol & Oncol, Incheon, South Korea
[15] Tongji Univ, Pulm Hosp, Shanghai, Peoples R China
[16] Jilin Prov Canc Hosp, Changchun, Jilin, Peoples R China
[17] Hosp Umum Sarawak, Kuching, Malaysia
[18] Natl Cheng Kung Univ, Tainan, Taiwan
[19] H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL USA
[20] Univ Coll London Hosp, Biomed Res Ctr, Dept Oncol, London, England
[21] Canc Res UK Lung Canc Ctr Excellence, London, England
[22] AstraZeneca, Cambridge, England
[23] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA
来源
NEW ENGLAND JOURNAL OF MEDICINE | 2018年 / 378卷 / 02期
关键词
OPEN-LABEL; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; PHASE-III; CNS RESPONSE; AZD9291; CHEMOTHERAPY; GEFITINIB; ERLOTINIB; THERAPY;
D O I
10.1056/NEJMoa1713137
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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收藏
页码:113 / 125
页数:13
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