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Crizotinib in ROS1-Rearranged Non-Small-Cell Lung Cancer

Cited 1074 time in Web of Science Cited 1118 time in Scopus
Authors
Shaw, Alice T.; Ou, Sai-Hong I.; Bang, Yung-Jue; Camidge, D. Ross; Solomon, Benjamin J.; Salgia, Ravi; Riely, Gregory J.; Varella-Garcia, Marileila; Shapiro, Geoffrey I.; Costa, Daniel B.; Doebele, Robert C.; Long Phi Le; Zheng, Zongli; Tan, Weiwei; Stephenson, Patricia; Shreeve, S. Martin; Tye, Lesley M.; Christensen, James G.; Wilner, Keith D.; Clark, Jeffrey W.; Iafrate, A. John
Issue Date
2014-11
Citation
New England Journal of Medicine, Vol.371 No.21, pp.1963-1971
Abstract
Background Chromosomal rearrangements of the gene encoding ROS1 proto-oncogene receptor tyrosine kinase (ROS1) define a distinct molecular subgroup of non-small-cell lung cancers (NSCLCs) that may be susceptible to therapeutic ROS1 kinase inhibition. Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET. Methods We enrolled 50 patients with advanced NSCLC who tested positive for ROS1 rearrangement in an expansion cohort of the phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg twice daily and assessed for safety, pharmacokinetics, and response to therapy. ROS1 fusion partners were identified with the use of next-generation sequencing or reverse-transcriptase-polymerase-chain-reaction assays. Results The objective response rate was 72% (95% confidence interval [CI], 58 to 84), with 3 complete responses and 33 partial responses. The median duration of response was 17.6 months (95% CI, 14.5 to not reached). Median progression-free survival was 19.2 months (95% CI, 14.4 to not reached), with 25 patients (50%) still in follow-up for progression. Among 30 tumors that were tested, we identified 7 ROS1 fusion partners: 5 known and 2 novel partner genes. No correlation was observed between the type of ROS1 rearrangement and the clinical response to crizotinib. The safety profile of crizotinib was similar to that seen in patients with ALK-rearranged NSCLC. Conclusions In this study, crizotinib showed marked antitumor activity in patients with advanced ROS1-rearranged NSCLC. ROS1 rearrangement defines a second molecular subgroup of NSCLC for which crizotinib is highly active.
ISSN
0028-4793
URI
https://hdl.handle.net/10371/173128
DOI
https://doi.org/10.1056/NEJMoa1406766
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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