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

摘要: Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup non–small-cell lung cancers, representing 2 to 7% such tumors. We explored the therapeutic efficacy inhibiting ALK tumors an early-phase clinical trial crizotinib (PF-02341066), orally available small-molecule inhibitor tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with cancer for presence rearrangements, we identified 82 advanced ALK-positive disease who were eligible trial. Most had received previous treatment. These enrolled expanded cohort study instituted after phase 1 dose escalation established recommended 250 mg twice daily 28-day cycles. Patients assessed adverse events response therapy. Results rearrangements tended be younger than those without most little or no exposure tobacco adenocarcinomas. At mean treatment duration 6.4 months, overall rate was 57% (47 patients, 46 confirmed partial responses complete response); 27 (33%) stable disease. A total 63 (77%) continuing receive at time data cutoff, estimated probability 6-month progression-free survival 72%, median reached. The drug resulted grade (mild) gastrointestinal side effects. Conclusions inhibition rearrangement shrinkage patients. (Funded by Pfizer others; ClinicalTrials.gov number, NCT00585195.)