About FDA


On August 26, 2011, the U. S. Food and Drug Administration granted accelerated approval to crizotinib (XALKORI Capsules, Pfizer Inc.) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The FDA approved the Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) concurrently with the crizotinib approval. This companion diagnostic test is designed to detect rearrangements of the anaplastic lymphoma kinase (ALK) gene in NSCLC.

The approval was based on two single arm trials, Study A (N = 136 patients) and Study B (N = 119 patients). Crizotinib, 250 mg, was administered orally twice daily to a total of 255 patients with locally advanced or metastatic ALK-positive NSCLC. Demographic analysis from the combined data of these trials noted that the median age was 52 years, 63% of patients were Caucasian, 30% were Asian, 48% were male and 84% had an ECOG performance status of 0 or 1. Fewer than 3% of patients were current smokers. Ninety-six percent had adenocarcinoma, 95% had metastatic disease, and 94% had received prior systemic treatment for NSCLC.  
The primary endpoint of both trials was objective response rate (ORR) as assessed by the investigator. In Study A, the ORR was 50% (95% CI: 42%, 59%) with a median response duration of 42 weeks. In Study B, the ORR was 61% (95% CI: 52%, 70%) with a median response duration of 48 weeks. Complete responses were observed in 1% of patients. No differences in ORR by performance status, the number of prior chemotherapeutic regimens, or the percentage of cells found to have the ALK gene rearrangement were noted.
The most common adverse reactions (≥25%) observed in both studies were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Vision disorders included visual impairment, photopsia, vision blurred, vitreous floaters, photophobia, and diplopia. Grade 3-4 adverse reactions in at least 4% of patients included increased ALT and neutropenia. Crizotinib has been associated with severe, life-threatening, or fatal treatment-related pneumonitis with a frequency of 1.6% in clinical trials. All cases occurred within 2 months after the treatment initiation.
The recommended dose and schedule for XALKORI is 250 mg orally twice daily.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Page Last Updated: 11/27/2015
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