FDA Approval for Crizotinib
Brand name: Xalkori®
- Approved for locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase-positive as detected by an FDA-approved test.
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On August 26, 2011, the Food and Drug Administration (FDA) granted accelerated approval to crizotinib (Xalkori Capsules, made by Pfizer, Inc.) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is 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 percent of patients were Caucasian, 30 percent were Asian, 48 percent were male and 84 percent had an ECOG performance status of 0 or 1. Fewer than 3 percent of patients were current smokers. Ninety-six percent had adenocarcinoma, 95 percent had metastatic disease, and 94 percent 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 percent (95 percent CI: 42 percent, 59 percent) with a median response duration of 42 weeks. In Study B, the ORR was 61 percent (95 percent CI: 52 percent, 70 percent) with a median response duration of 48 weeks. Complete responses were observed in 1 percent of patients. No differences in ORR by performance status, number of prior chemotherapeutic regimens, or percentage of cells found to have the ALK gene rearrangement were noted.
The most common adverse reactions (at least 25 percent) 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 percent 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 percent in clinical trials. All cases occurred within 2 months after the treatment initiation.
The recommended dose and schedule for crizotinib is 250 mg orally twice daily.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.