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AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer

Cited 1236 time in Web of Science Cited 1323 time in Scopus
Authors
Jaenne, Pasi A.; Yang, James Chih-Hsin; Kim, Dong-Wan; Planchard, David; Ohe, Yuichiro; Ramalingam, Suresh S.; Ahn, Myung-Ju; Kim, Sang-We; Su, Wu-Chou; Horn, Leora; Haggstrom, Daniel; Felip, Enriqueta; Kim, Joo-Hang; Frewer, Paul; Cantarini, Mireille; Brown, Kathryn H.; Dickinson, Paul A.; Ghiorghiu, Serban; Ranson, Malcolm
Issue Date
2015-04
Citation
New England Journal of Medicine, Vol.372 No.18, pp.1689-1699
Abstract
BACKGROUND The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. METHODS We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy. RESULTS A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients. CONCLUSIONS AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors.
ISSN
0028-4793
URI
http://hdl.handle.net/10371/165380
DOI
https://doi.org/10.1056/NEJMoa1411817
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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