Eunice L. Kwak, M.D., Ph.D., Yung-Jue Bang, M.D., Ph.D., D. Ross Camidge, M.D., Ph.D., Alice T. Shaw, M.D., Ph.D., Benjamin Solomon, M.B., B.S., Ph.D., Robert G. Maki, M.D., Ph.D., Sai-Hong I. Ou, M.D., Ph.D., Bruce J. Dezube, M.D., Pasi A. Jänne, M.D., Ph.D., Daniel B. Costa, M.D., Ph.D., Marileila Varella-Garcia, Ph.D., Woo-Ho Kim, M.D., Thomas J. Lynch, M.D., Panos Fidias, M.D., Hannah Stubbs, M.S., Jeffrey A. Engelman, M.D., Ph.D., Lecia V. Sequist, M.D., M.P.H., WeiWei Tan, Ph.D., Leena Gandhi, M.D., Ph.D., Mari Mino-Kenudson, M.D., Greg C. Wei, Ph.D., S. Martin Shreeve, M.D., Ph.D., Mark J. Ratain, M.D., Jeffrey Settleman, Ph.D., James G. Christensen, Ph.D., Daniel A. Haber, M.D., Ph.D., Keith Wilner, Ph.D., Ravi Salgia, M.D., Ph.D., Geoffrey I. Shapiro, M.D., Ph.D., Jeffrey W. Clark, M.D., and A. John Iafrate, M.D., Ph.D. N Engl J Med 2010; 363:1693-1703, October 28, 2010
Background
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. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)
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