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. (Funded by 
Pfizer and others; ClinicalTrials.gov number, NCT00585195.).