Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

被引：2176

作者：

Ramalingam, S. S. ^{[1
]}

Vansteenkiste, J. ^{[2
]}

Planchard, D. ^{[3
]}

Cho, B. C. ^{[5
]}

Gray, J. E. ^{[7
]}

Ohe, Y. ^{[8
]}

Zhou, C. ^{[11
]}

Reungwetwattana, T.

Cheng, Y. ^{[12
]}

Chewaskulyong, B. ^{[13
]}

Shah, R. ^{[14
,15
]}

Cobo, M. ^{[18
]}

Lee, K. H. ^{[6
]}

Cheema, P. ^{[19
]}

Tiseo, M. ^{[20
,21
]}

John, T. ^{[22
]}

Lin, M-C ^{[23
]}

Imamura, F. ^{[9
]}

Kurata, T. ^{[10
]}

Todd, A. ^{[16
]}

Hodge, R. ^{[16
]}

Saggese, M. ^{[17
]}

Rukazenkov, Y. ^{[17
]}

Soria, J-C ^{[3
,4
,24
]}

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] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA

[2] Katholieke Univ Leuven, Univ Hosp, Dept Resp Med, Resp Oncol Unit, Leuven, Belgium

[3] Inst Gustave Roussy, Dept Med Oncol, Thorac Unit, Villejuif, France

[4] Univ Paris Sud, Orsay, France

[5] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Dept Internal Med,Div Med Oncol, Seoul, South Korea

[6] Chungbuk Natl Univ, Chungbuk Natl Univ Hosp, Coll Med, Div Med Oncol, Cheongju, South Korea

[7] H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL USA

[8] Natl Canc Ctr, Dept Thorac Oncol, Tokyo, Japan

[9] Osaka Int Canc Inst, Dept Thorac Oncol, Osaka, Japan

[10] Kansai Med Univ Hosp, Dept Thorac Oncol, Osaka, Japan

[11] Tongji Univ, Pulm Hosp, Shanghai, Peoples R China

[12] Jilin Prov Canc Hosp, Changchun, Jilin, Peoples R China

[13] Chiang Mai Univ, Dept Med, Oncol Unit, Chiang Mai, Thailand

[14] Maidstone Hlth Author, Kent Oncol Ctr, Maidstone, Kent, England

[15] Tunbridge Wells NHS Trust, Maidstone, Kent, England

[16] AstraZeneca, Late Oncol Stat, Cambridge, England

[17] AstraZeneca, Oncol Res & Dev, Cambridge, England

[18] Hosp Reg Univ Malaga, Inst Invest Biomed Malaga, Malaga, Spain

[19] Univ Toronto, William Osier Hlth Syst, Toronto, ON, Canada

[20] Univ Parma, Dept Med & Surg, Parma, Italy

[21] Univ Hosp Parma, Med Oncol Unit, Parma, Italy

[22] Austin Hlth, Dept Med Oncol, Melbourne, Vic, Australia

[23] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Coll Med, Dept Internal Med,Div Pulm & Crit Care Med, Kaohsiung, Taiwan

[24] AstraZeneca, Early Oncol Res & Dev, Gaithersburg, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 382卷 / 01期

关键词：

CELL LUNG-CANCER; GEFITINIB; CHEMOTHERAPY; ERLOTINIB; AFATINIB; THERAPY; PLACEBO; TRIAL;

D O I：

10.1056/NEJMoa1913662

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. Methods In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. Results The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P=0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. Conclusions Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.)

引用

页码：41 / 50

页数：10

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