FDA Approves Crizotinib [Xalkori] with Companion Diagnostic Test for Non-Small Cell Lung Cancers (NSCLC) Positive for the Anaplastic Lymphoma Kinase (ALK) Gene

Last Updated on January 25, 2015 by Joseph Gut – thasso

August 26, 2011 – Today, the  American Food and Drug Administration (FDA) has approved Crizotinib [Xalkori] to treat the patient subgroup with late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) whos cancers express (i.e., test positive for the presence of) the abnormal anaplastic lymphoma kinase (ALK) gene.

The abnormal anaplastic lymphoma kinase (ALK) gene causes cancer cell development and growth. About 1 percent to 7 percent of the patients with NSCLC have the ALK gene abnormality. Patients with this form of lung cancer are typically non-smokers. Crizotinib [Xalkori] works by blocking certain proteins called kinases, including the protein produced by the abnormal ALK gene. Xalkori is a pill taken twice a day as a single-agent treatment.

Crizotinib [Xalkori] has been approved together with a companion diagnostic test that will help determine if a patient’s tumor expresses the abnormal ALK gene. This genetic test is called the Vysis ALK Break Apart FISH Probe Kit. The application of this specific test allows the selection of only those  patients for treatment with Crizotinib [Xalkori] who are most likely to respond to the drug. Targeted therapies such as this one invoving Crizotinib [Xalkori] are considered important options for sucessfully treating patients with this disease.

Crizotinib [Xalkori]’s effectiveness was established in two multi-center, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. A sample of a patient’s lung cancer tissue was collected and tested for the ALK gene abnormality prior to study enrollment. The studies were designed to measure objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy. In one study, the objective response rate was 50 percent with a median response duration of 42 weeks. In another study, the objective response rate was 61 percent with a median response duration of 48 weeks.

Based on these favorable efficacy data, Crizotinib [Xalkori] has been approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious  and life-threatening disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, followed by further studies to confirm the drug’s clinical benefit.

The most common side effects reported in patients receiving Crizotinib [Xalkori] included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects. Xalkori use has also been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. Patients with treatment-related pneumonitis should permanently stop treatment with Crizotinib [Xalkori]. Moreover, the drug should not be used in pregnant women. In the context of the clinical safety of Crizotinib [Xalkori], we should be aware that the companion test (Vysis ALK Break Apart FISH Probe Kit) does not identify patients with either a predisposition for any of the unwanted drug side effects, or irregularities in drug disposition (e.g., poor or ultrarapid metabolizers). We will also need many more patients treated with Crizotinib [Xalkori] in order to more completely understand the clinical safety profile of Crizotinib [Xalkori].

See the FDA Press Release here.