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Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer

Cited 3225 time in Web of Science Cited 3518 time in Scopus
Authors
Kwak, Eunice L.; Bang, Yung-Jue; Camidge, D. Ross; Shaw, Alice T.; Solomon, Benjamin; Maki, Robert G.; Ou, Sai-Hong I.; Dezube, Bruce J.; Jaenne, Pasi A.; Costa, Daniel B.; Varella-Garcia, Marileila; Kim, Woo-Ho; Lynch, Thomas J.; Fidias, Panos; Stubbs, Hannah; Engelman, Jeffrey A.; Sequist, Lecia V.; Tan, WeiWei; Gandhi, Leena; Mino-Kenudson, Mari; Wei, Greg C.; Shreeve, S. Martin; Ratain, Mark J.; Settleman, Jeffrey; Christensen, James G.; Haber, Daniel A.; Wilner, Keith; Salgia, Ravi; Shapiro, Geoffrey I.; Clark, Jeffrey W.; Iafrate, A. John
Issue Date
2010-10
Citation
New England Journal of Medicine, Vol.363 No.18, pp.1693-1703
Abstract
BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. METHODS After screening tumor samples from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. RESULTS Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients.
ISSN
0028-4793
URI
https://hdl.handle.net/10371/173123
DOI
https://doi.org/10.1056/NEJMoa1006448
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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